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1. Copy number architectures define treatment-mediated selection of lethal prostate cancer clones

Author

Hasan, A, Cremaschi, P, Wetterskog, D, Jayaram, A, Wong, S, Williams, S, Pasam, A, Trigos, A, Trujillo, B, Grist, E, Friedrich, S, Vainauskas, O, Parry, M, Ismail, M, Devlies, W, Wingate, A, Linch, M, Naceur-Lombardelli, C, Zaccaria, S, Hessey, S, Shiu, K, Bridgewater, J, Hochhauser, D, Forster, M, Lee, S, Ahmad, T, Papadatos-Pastos, D, Janes, S, Van Loo, P, Enfield, K, Mcgranahan, N, Huebner, A, Quezada, S, Beck, S, Parker, P, Enver, T, Hynds, R, Pearce, D, Falzon, M, Proctor, I, Sinclair, R, Lok, C, Rhodes, Z, Moore, D, Marafioti, T, Mitchison, M, Ellery, P, Sivakumar, M, Brandner, S, Rowan, A, Hiley, C, Veeriah, S, Shaw, H, Toncheva, A, Prymas, P, Watkins, T, Bailey, C, Martinez Ruiz, C, Litchfield, K, Al-Bakir, M, Kanu, N, Ward, S, Lim, E, Reading, J, Chain, B, Akay, M, Flanagan, A, Biswas, D, Pich, O, Dietzen, M, Puttick, C, Colliver, E, Magness, A, Angelova, M, Black, J, Lucas, O, Hill, W, Liu, W, Frankell, A, Magno, N, Athanasopoulou, F, Salgado, R, Lee, C, Grigoriadis, K, Al-Sawaf, O, Karasaki, T, Bunkum, A, Noorani, I, Benafif, S, Barbe, V, Bola, S, Leone, G, Alifrangis, C, Mcgovern, U, Thol, K, Gamble, S, Ung, S, Sahwangarrom, T, Marin, C, Pawlik, P, Lam, J, Richard, C, Vendramin, R, Dijkstra, K, Rane, J, Nicod, J, Dwornik, A, Bowles, K, Zaidi, R, Gishen, F, Stone, P, Stirling, C, Turajlic, S, Larkin, J, Pickering, L, Furness, A, Young, K, Drake, W, Edmonds, K, Hunter, N, Mangwende, M, Pearce, K, Grostate, L, Au, L, Spain, L, Shepherd, S, Yan, H, Shum, B, Tippu, Z, Hanley, B, Spencer, C, Emmerich, M, Gerard, C, Schmitt, A, Del Rosario, L, Carlyle, E, Lewis, C, Holt, L, Lucanas, A, O'Flaherty, M, Hazell, S, Mudhar, H, Messiou, C, Latifoltojar, A, Fendler, A, Byrne, F, Pallikonda, H, Lobon, I, Coulton, A, Cattin, A, Deng, D, Feng, H, Yousaf, N, Popat, S, Curtis, O, Milner-Watts, C, Stamp, G, Nye, E, Murra, A, Korteweg, J, Kelly, D, Terry, L, Biano, J, Peat, K, Kelly, K, Grieco, C, Le, M, D'Arienzo, P, Turay, E, Hill, P, Josephs, D, Irshad, S, Spicer, J, Mahadeva, U, Green, A, Stewart, R, Wright, N, Pulman, G, Mitu, R, Phillips-Boyd, S, Enting, D, Rudman, S, Ghosh, S, Karapanagiotou, E, Pintus, E, Tutt, A, Howlett, S, Brenton, J, Caldas, C, Fitzgerald, R, Jimenez-Linan, M, Provenzano, E, Cluroe, A, Paterson, A, Aitken, S, Allinson, K, Stewart, G, Mcdermott, U, Beddowes, E, Maughan, T, Ansorge, O, Campbell, P, Roxburgh, P, Fraser, S, Blyth, K, Le Quesne, J, Krebs, M, Blackhall, F, Summers, Y, Oliveira, P, Ortega-Franco, A, Dive, C, Gomes, F, Carter, M, Dransfield, J, Thomas, A, Fennell, D, Shaw, J, Wilson, C, Marrone, D, Naidu, B, Baijal, S, Tanchel, B, Langman, G, Robinson, A, Collard, M, Cockcroft, P, Ferris, C, Bancroft, H, Kerr, A, Middleton, G, Webb, J, Kadiri, S, Colloby, P, Olisemeke, B, Wilson, R, Shackleford, H, Osman, A, Tomlinson, I, Jogai, S, Holden, S, Fernandes, T, Mcneish, I, Hampton, B, Mckenzie, M, Hackshaw, A, Sharp, A, Chan, K, Farrelly, L, Bridger, H, Leslie, R, Tookman, A, Swanton, C, Jamal-Hanjani, M, Lise, S, Sandhu, S, Attard, G, Hasan A. M. M., Cremaschi P., Wetterskog D., Jayaram A., Wong S. Q., Williams S., Pasam A., Trigos A., Trujillo B., Grist E., Friedrich S., Vainauskas O., Parry M., Ismail M., Devlies W., Wingate A., Linch M., Naceur-Lombardelli C., Zaccaria S., Hessey S., Shiu K. -K., Bridgewater J., Hochhauser D., Forster M., Lee S. -M., Ahmad T., Papadatos-Pastos D., Janes S., Van Loo P., Enfield K., McGranahan N., Huebner A., Quezada S., Beck S., Parker P., Enver T., Hynds R. E., Pearce D. R., Falzon M., Proctor I., Sinclair R., Lok C. -W., Rhodes Z., Moore D., Marafioti T., Mitchison M., Ellery P., Sivakumar M., Brandner S., Rowan A., Hiley C., Veeriah S., Shaw H., Toncheva A., Prymas P., Watkins T. B. K., Bailey C., Martinez Ruiz C., Litchfield K., Al-Bakir M., Kanu N., Ward S., Lim E., Reading J., Chain B., Watkins T., Akay M., Flanagan A., Biswas D., Pich O., Dietzen M., Puttick C., Colliver E., Magness A., Angelova M., Black J., Lucas O., Hill W., Liu W. -K., Frankell A., Magno N., Athanasopoulou F., Salgado R., Lee C., Grigoriadis K., Al-Sawaf O., Karasaki T., Bunkum A., Noorani I., Benafif S., Barbe V., Bola S. K., Leone G., Alifrangis C., McGovern U., Thol K., Gamble S., Ung S. K., Sahwangarrom T., Marin C. P., Wong S., Pawlik P., Lam J. M., Richard C., Vendramin R., Dijkstra K., Rane J., Nicod J., Dwornik A., Bowles K., Zaidi R., Gishen F., Stone P., Stirling C., Turajlic S., Larkin J., Pickering L., Furness A., Young K., Drake W., Edmonds K., Hunter N., Mangwende M., Pearce K., Grostate L., Au L., Spain L., Shepherd S., Yan H., Shum B., Tippu Z., Hanley B., Spencer C., Emmerich M., Gerard C., Schmitt A. M., Del Rosario L., Carlyle E., Lewis C., Holt L., Lucanas A., O'Flaherty M., Hazell S., Mudhar H., Messiou C., Latifoltojar A., Fendler A., Byrne F., Pallikonda H., Lobon I., Coulton A., Cattin A. -L., Deng D., Feng H., Yousaf N., Popat S., Curtis O., Milner-Watts C., Stamp G., Nye E., Murra A., Korteweg J., Kelly D., Terry L., Biano J., Peat K., Kelly K., Grieco C., Le M. L., D'Arienzo P. D., Turay E., Hill P., Josephs D., Irshad S., Spicer J., Mahadeva U., Green A., Stewart R., Wright N., Pulman G., Mitu R., Phillips-Boyd S., Enting D., Rudman S., Ghosh S., Karapanagiotou E., Pintus E., Tutt A., Howlett S., Brenton J., Caldas C., Fitzgerald R., Jimenez-Linan M., Provenzano E., Cluroe A., Paterson A., Aitken S., Allinson K., Stewart G., McDermott U., Beddowes E., Maughan T., Ansorge O., Campbell P., Roxburgh P., Fraser S., Blyth K., Le Quesne J., Krebs M., Blackhall F., Summers Y., Oliveira P., Ortega-Franco A., Dive C., Gomes F., Carter M., Dransfield J., Thomas A., Fennell D., Shaw J., Wilson C., Marrone D., Naidu B., Baijal S., Tanchel B., Langman G., Robinson A., Collard M., Cockcroft P., Ferris C., Bancroft H., Kerr A., Middleton G., Webb J., Kadiri S., Colloby P., Olisemeke B., Wilson R., Shackleford H., Osman A., Tomlinson I., Jogai S., Holden S., Fernandes T., McNeish I., Hampton B., McKenzie M., Hackshaw A., Sharp A., Chan K., Farrelly L., Bridger H., Leslie R., Tookman A., Swanton C., Jamal-Hanjani M., Lise S., Sandhu S., Attard G., Hasan, A, Cremaschi, P, Wetterskog, D, Jayaram, A, Wong, S, Williams, S, Pasam, A, Trigos, A, Trujillo, B, Grist, E, Friedrich, S, Vainauskas, O, Parry, M, Ismail, M, Devlies, W, Wingate, A, Linch, M, Naceur-Lombardelli, C, Zaccaria, S, Hessey, S, Shiu, K, Bridgewater, J, Hochhauser, D, Forster, M, Lee, S, Ahmad, T, Papadatos-Pastos, D, Janes, S, Van Loo, P, Enfield, K, Mcgranahan, N, Huebner, A, Quezada, S, Beck, S, Parker, P, Enver, T, Hynds, R, Pearce, D, Falzon, M, Proctor, I, Sinclair, R, Lok, C, Rhodes, Z, Moore, D, Marafioti, T, Mitchison, M, Ellery, P, Sivakumar, M, Brandner, S, Rowan, A, Hiley, C, Veeriah, S, Shaw, H, Toncheva, A, Prymas, P, Watkins, T, Bailey, C, Martinez Ruiz, C, Litchfield, K, Al-Bakir, M, Kanu, N, Ward, S, Lim, E, Reading, J, Chain, B, Akay, M, Flanagan, A, Biswas, D, Pich, O, Dietzen, M, Puttick, C, Colliver, E, Magness, A, Angelova, M, Black, J, Lucas, O, Hill, W, Liu, W, Frankell, A, Magno, N, Athanasopoulou, F, Salgado, R, Lee, C, Grigoriadis, K, Al-Sawaf, O, Karasaki, T, Bunkum, A, Noorani, I, Benafif, S, Barbe, V, Bola, S, Leone, G, Alifrangis, C, Mcgovern, U, Thol, K, Gamble, S, Ung, S, Sahwangarrom, T, Marin, C, Pawlik, P, Lam, J, Richard, C, Vendramin, R, Dijkstra, K, Rane, J, Nicod, J, Dwornik, A, Bowles, K, Zaidi, R, Gishen, F, Stone, P, Stirling, C, Turajlic, S, Larkin, J, Pickering, L, Furness, A, Young, K, Drake, W, Edmonds, K, Hunter, N, Mangwende, M, Pearce, K, Grostate, L, Au, L, Spain, L, Shepherd, S, Yan, H, Shum, B, Tippu, Z, Hanley, B, Spencer, C, Emmerich, M, Gerard, C, Schmitt, A, Del Rosario, L, Carlyle, E, Lewis, C, Holt, L, Lucanas, A, O'Flaherty, M, Hazell, S, Mudhar, H, Messiou, C, Latifoltojar, A, Fendler, A, Byrne, F, Pallikonda, H, Lobon, I, Coulton, A, Cattin, A, Deng, D, Feng, H, Yousaf, N, Popat, S, Curtis, O, Milner-Watts, C, Stamp, G, Nye, E, Murra, A, Korteweg, J, Kelly, D, Terry, L, Biano, J, Peat, K, Kelly, K, Grieco, C, Le, M, D'Arienzo, P, Turay, E, Hill, P, Josephs, D, Irshad, S, Spicer, J, Mahadeva, U, Green, A, Stewart, R, Wright, N, Pulman, G, Mitu, R, Phillips-Boyd, S, Enting, D, Rudman, S, Ghosh, S, Karapanagiotou, E, Pintus, E, Tutt, A, Howlett, S, Brenton, J, Caldas, C, Fitzgerald, R, Jimenez-Linan, M, Provenzano, E, Cluroe, A, Paterson, A, Aitken, S, Allinson, K, Stewart, G, Mcdermott, U, Beddowes, E, Maughan, T, Ansorge, O, Campbell, P, Roxburgh, P, Fraser, S, Blyth, K, Le Quesne, J, Krebs, M, Blackhall, F, Summers, Y, Oliveira, P, Ortega-Franco, A, Dive, C, Gomes, F, Carter, M, Dransfield, J, Thomas, A, Fennell, D, Shaw, J, Wilson, C, Marrone, D, Naidu, B, Baijal, S, Tanchel, B, Langman, G, Robinson, A, Collard, M, Cockcroft, P, Ferris, C, Bancroft, H, Kerr, A, Middleton, G, Webb, J, Kadiri, S, Colloby, P, Olisemeke, B, Wilson, R, Shackleford, H, Osman, A, Tomlinson, I, Jogai, S, Holden, S, Fernandes, T, Mcneish, I, Hampton, B, Mckenzie, M, Hackshaw, A, Sharp, A, Chan, K, Farrelly, L, Bridger, H, Leslie, R, Tookman, A, Swanton, C, Jamal-Hanjani, M, Lise, S, Sandhu, S, Attard, G, Hasan A. M. M., Cremaschi P., Wetterskog D., Jayaram A., Wong S. Q., Williams S., Pasam A., Trigos A., Trujillo B., Grist E., Friedrich S., Vainauskas O., Parry M., Ismail M., Devlies W., Wingate A., Linch M., Naceur-Lombardelli C., Zaccaria S., Hessey S., Shiu K. -K., Bridgewater J., Hochhauser D., Forster M., Lee S. -M., Ahmad T., Papadatos-Pastos D., Janes S., Van Loo P., Enfield K., McGranahan N., Huebner A., Quezada S., Beck S., Parker P., Enver T., Hynds R. E., Pearce D. R., Falzon M., Proctor I., Sinclair R., Lok C. -W., Rhodes Z., Moore D., Marafioti T., Mitchison M., Ellery P., Sivakumar M., Brandner S., Rowan A., Hiley C., Veeriah S., Shaw H., Toncheva A., Prymas P., Watkins T. B. K., Bailey C., Martinez Ruiz C., Litchfield K., Al-Bakir M., Kanu N., Ward S., Lim E., Reading J., Chain B., Watkins T., Akay M., Flanagan A., Biswas D., Pich O., Dietzen M., Puttick C., Colliver E., Magness A., Angelova M., Black J., Lucas O., Hill W., Liu W. -K., Frankell A., Magno N., Athanasopoulou F., Salgado R., Lee C., Grigoriadis K., Al-Sawaf O., Karasaki T., Bunkum A., Noorani I., Benafif S., Barbe V., Bola S. K., Leone G., Alifrangis C., McGovern U., Thol K., Gamble S., Ung S. K., Sahwangarrom T., Marin C. P., Wong S., Pawlik P., Lam J. M., Richard C., Vendramin R., Dijkstra K., Rane J., Nicod J., Dwornik A., Bowles K., Zaidi R., Gishen F., Stone P., Stirling C., Turajlic S., Larkin J., Pickering L., Furness A., Young K., Drake W., Edmonds K., Hunter N., Mangwende M., Pearce K., Grostate L., Au L., Spain L., Shepherd S., Yan H., Shum B., Tippu Z., Hanley B., Spencer C., Emmerich M., Gerard C., Schmitt A. M., Del Rosario L., Carlyle E., Lewis C., Holt L., Lucanas A., O'Flaherty M., Hazell S., Mudhar H., Messiou C., Latifoltojar A., Fendler A., Byrne F., Pallikonda H., Lobon I., Coulton A., Cattin A. -L., Deng D., Feng H., Yousaf N., Popat S., Curtis O., Milner-Watts C., Stamp G., Nye E., Murra A., Korteweg J., Kelly D., Terry L., Biano J., Peat K., Kelly K., Grieco C., Le M. L., D'Arienzo P. D., Turay E., Hill P., Josephs D., Irshad S., Spicer J., Mahadeva U., Green A., Stewart R., Wright N., Pulman G., Mitu R., Phillips-Boyd S., Enting D., Rudman S., Ghosh S., Karapanagiotou E., Pintus E., Tutt A., Howlett S., Brenton J., Caldas C., Fitzgerald R., Jimenez-Linan M., Provenzano E., Cluroe A., Paterson A., Aitken S., Allinson K., Stewart G., McDermott U., Beddowes E., Maughan T., Ansorge O., Campbell P., Roxburgh P., Fraser S., Blyth K., Le Quesne J., Krebs M., Blackhall F., Summers Y., Oliveira P., Ortega-Franco A., Dive C., Gomes F., Carter M., Dransfield J., Thomas A., Fennell D., Shaw J., Wilson C., Marrone D., Naidu B., Baijal S., Tanchel B., Langman G., Robinson A., Collard M., Cockcroft P., Ferris C., Bancroft H., Kerr A., Middleton G., Webb J., Kadiri S., Colloby P., Olisemeke B., Wilson R., Shackleford H., Osman A., Tomlinson I., Jogai S., Holden S., Fernandes T., McNeish I., Hampton B., McKenzie M., Hackshaw A., Sharp A., Chan K., Farrelly L., Bridger H., Leslie R., Tookman A., Swanton C., Jamal-Hanjani M., Lise S., Sandhu S., and Attard G.

Abstract

Despite initial responses to hormone treatment, metastatic prostate cancer invariably evolves to a lethal state. To characterize the intra-patient evolutionary relationships of metastases that evade treatment, we perform genome-wide copy number profiling and bespoke approaches targeting the androgen receptor (AR) on 167 metastatic regions from 11 organs harvested post-mortem from 10 men who died from prostate cancer. We identify diverse and patient-unique alterations clustering around the AR in metastases from every patient with evidence of independent acquisition of related genomic changes within an individual and, in some patients, the co-existence of AR-neutral clones. Using the genomic boundaries of pan-autosome copy number changes, we confirm a common clone of origin across metastases and diagnostic biopsies, and identified in individual patients, clusters of metastases occupied by dominant clones with diverged autosomal copy number alterations. These autosome-defined clusters are characterized by cluster-specific AR gene architectures, and in two index cases are topologically more congruent than by chance (p-values 3.07 × 10−8 and 6.4 × 10−4). Integration with anatomical sites suggests patterns of spread and points of genomic divergence. Here, we show that copy number boundaries identify treatment-selected clones with putatively distinct lethal trajectories.

Published
2023

2. Immune responses following third COVID-19 vaccination are reduced in patients with hematological malignancies compared to patients with solid

Author

Fendler, A, Shepherd, STC, Au, L, Wilkinson, KA, Wu, M, Schmitt, AM, Tippu, Z, Farag, S, Rogiers, A, Harvey, R, Carlyle, E, Edmonds, K, Del Rosario, L, Lingard, K, Mangwende, M, Holt, L, Ahmod, H, Korteweg, J, Foley, T, Barber, T, Emslie-Henry, A, Caulfield-Lynch, N, Byrne, F, Shum, B, Gerard, CL, Deng, D, Kjaer, S, Song, O-R, Queval, C, Kavanagh, C, Wall, EC, Carr, EJ, Namjou, S, Caidan, S, Gavrielides, M, MacRae, JI, Kelly, G, Peat, K, Kelly, D, Murra, A, Kelly, K, O'Flaherty, M, Shea, RL, Gardner, G, Murray, D, Popat, S, Yousaf, N, Jhanji, S, Van As, N, Young, K, Furness, AJS, Pickering, L, Beale, R, Swanton, C, Crick COVID19 consortium, Gandhi, S, Gamblin, S, Bauer, DLV, Kassiotis, G, Howell, M, Nicholson, E, Walker, S, Wilkinson, RJ, Larkin, J, Turajlic, S, CAPTURE consortium, and Wellcome Trust

Subjects
Cancer Research, Crick COVID19 consortium, Oncology, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, 1109 Neurosciences, CAPTURE consortium
Abstract

In this report from the CAPTURE study (NCT03226886), we demonstrate that a third dose of COVID-19 vaccine boosts neutralizing antibody (NAb) and cellular responses in patients with cancer, including those that had undetectable NAb titers (NAbT) following two vaccine doses or for whom NAbT waned. We have noted that one key member of the CAPTURE consortium—Sanjay Popat—was inadvertently not included in the author list. We now include him as a co-author. There are no additional changes to the declaration of interests statement, since Dr. Popat declares no competing conflict of interest. This author list change is now reflected in the online version of this letter.

Published
2022
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3. Growth, physical, and cognitive function in children who are born HIV-free: School-age follow-up of a cluster-randomised trial in rural Zimbabwe.

Author

Piper JD, Mazhanga C, Mwapaura M, Mapako G, Mapurisa I, Mashedze T, Munyama E, Kuona M, Mashiri T, Sibanda K, Matemavi D, Tichagwa M, Nyoni S, Saidi A, Mangwende M, Chidhanguro D, Mpofu E, Tome J, Mbewe G, Mutasa B, Chasekwa B, Njovo H, Nyachowe C, Muchekeza M, Mutasa K, Sauramba V, Evans C, Gladstone MJ, Wells JC, Allen E, Smuk M, Humphrey JH, Langhaug LF, Tavengwa NV, Ntozini R, and Prendergast AJ

Subjects
Humans, Female, Zimbabwe, Male, Pregnancy, Child, Follow-Up Studies, Infant, Pregnancy Complications, Infectious, Cognition, HIV Infections prevention & control, Rural Population, Child Development
Abstract

Background: Globally, over 16 million children were exposed to HIV during pregnancy but remain HIV-free at birth and throughout childhood by 2022. Children born HIV-free (CBHF) have higher morbidity and mortality and poorer neurodevelopment in early life compared to children who are HIV-unexposed (CHU), but long-term outcomes remain uncertain. We characterised school-age growth, cognitive and physical function in CBHF and CHU previously enrolled in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe., Methods and Findings: The SHINE trial enrolled pregnant women between 2012 and 2015 across 2 rural Zimbabwean districts. Co-primary outcomes were height-for-age Z-score and haemoglobin at age 18 months (clinicaltrials.gov NCT01824940). Children were re-enrolled if they were aged 7 years, resident in Shurugwi district, and had known pregnancy HIV-exposure status. From 5,280 pregnant women originally enrolled, 376 CBHF and 2016 CHU reached the trial endpoint at 18 months in Shurugwi; of these, 264 CBHF and 990 CHU were evaluated at age 7 years using the School-Age Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox. Cognitive function was evaluated using the Kaufman Assessment Battery for Children (KABC-II), with additional tools measuring executive function, literacy, numeracy, fine motor skills, and socioemotional function. Physical function was assessed using standing broad jump and handgrip for strength, and the shuttle-run test for cardiovascular fitness. Growth was assessed by anthropometry. Body composition was assessed by bioimpedance analysis and skinfold thicknesses. A caregiver questionnaire measured demographics, socioeconomic status, nurturing, child discipline, food, and water insecurity. We prespecified the primary comparisons and used generalised estimating equations with an exchangeable working correlation structure to account for clustering. Adjusted models used covariates from the trial (study arm, study nurse, exact child age, sex, calendar month measured, and ambient temperature). They also included covariates derived from directed acyclic graphs, with separate models adjusted for contemporary variables (socioeconomic status, household food insecurity, religion, social support, gender norms, caregiver depression, age, caregiver education, adversity score, and number of children's books) and early-life variables (length-for-age-Z-score) at 18 months, birthweight, maternal baseline depression, household diet, maternal schooling and haemoglobin, socioeconomic status, facility birth, and gender norms. We applied a Bonferroni correction for the 27 comparisons (0.05/27) with threshold of p < 0.00185 as significant. We found strong evidence that cognitive function was lower in CBHF compared to CHU across multiple domains. The KABC-II mental processing index was 45.2 (standard deviation (SD) 10.5) in CBHF and 48.3 (11.3) in CHU (mean difference 3.3 points [95% confidence interval (95% CI) 2.0, 4.5]; p < 0.001). The school achievement test score was 39.0 (SD 26.0) in CBHF and 45.7 (27.8) in CHU (mean difference 7.3 points [95% CI 3.6, 10.9]; p < 0.001); differences remained significant in adjusted analyses. Executive function was reduced but not significantly in adjusted analyses. We found no consistent evidence of differences in growth or physical function outcomes. The main limitation of our study was the restriction to one of two previous study districts, with possible survivor and selection bias., Conclusions: In this study, we found that CBHF had reductions in cognitive function compared to CHU at 7 years of age across multiple domains. Further research is needed to define the biological and psychosocial mechanisms underlying these differences to inform future interventions that help CBHF thrive across the life-course., Trial Registration: ClinicalTrials.gov The SHINE follow-up study was registered with the Pan-African Clinical Trials Registry (PACTR202201828512110). The original SHINE trial was registered at NCT https://clinicaltrials.gov/study/NCT01824940., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Piper et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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4. The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial: Protocol for school-age follow-up.

Author

Piper JD, Mazhanga C, Mwapaura M, Mapako G, Mapurisa I, Mashedze T, Munyama E, Kuona M, Mashiri T, Sibanda K, Matemavi D, Tichagwa M, Nyoni S, Saidi A, Mangwende M, Chidhanguro D, Mpofu E, Tome J, Mutasa B, Chasekwa B, Smuk M, Smith LE, Njovo H, Nyachowe C, Muchekeza M, Mutasa K, Sauramba V, Langhaug LF, Tavengwa NV, Gladstone MJ, Wells JC, Allen E, Humphrey JH, Ntozini R, and Prendergast AJ

Abstract

Background : There is a need for follow-up of early-life stunting intervention trials into childhood to determine their long-term impact. A holistic school-age assessment of health, growth, physical and cognitive function will help to comprehensively characterise the sustained effects of early-life interventions. Methods: The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe assessed the effects of improved infant and young child feeding (IYCF) and/or improved water, sanitation and hygiene (WASH) on stunting and anaemia at 18 months. Among children enrolled to SHINE, 1,275 have been followed up at 7-8 years of age (1,000 children who have not been exposed to HIV, 268 exposed to HIV antenatally who remain HIV negative and 7 HIV positive children). Children were assessed using the School-Age Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox, to measure their growth, body composition, cognitive and physical function. In parallel, a caregiver questionnaire assessed household demographics, socioeconomic status, adversity, nurturing, caregiver support, food and water insecurity. A monthly morbidity questionnaire is currently being administered by community health workers to evaluate school-age rates of infection and healthcare-seeking. The impact of the SHINE IYCF and WASH interventions, the early-life 'exposome', maternal HIV, and contemporary exposures on each school-age outcome will be assessed. We will also undertake an exploratory factor analysis to generate new, simpler metrics for assessment of cognition (COG-SAHARAN), growth (GROW-SAHARAN) and combined growth, cognitive and physical function (SUB-SAHARAN). The SUB-SAHARAN toolbox will be used to conduct annual assessments within the SHINE cohort from ages 8-12 years. Ethics and dissemination: Approval was obtained from Medical Research Council of Zimbabwe (08/02/21) and registered with Pan-African Clinical Trials Registry (PACTR202201828512110, 24/01/22). Primary caregivers provided written informed consent and children written assent. Findings will be disseminated through community sensitisation, peer-reviewed journals and stakeholders including the Zimbabwean Ministry of Health and Child Care., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Piper JD et al.)

Published
2023
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5. Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways.

Author

Spain L, Coulton A, Lobon I, Rowan A, Schnidrig D, Shepherd STC, Shum B, Byrne F, Goicoechea M, Piperni E, Au L, Edmonds K, Carlyle E, Hunter N, Renn A, Messiou C, Hughes P, Nobbs J, Foijer F, van den Bos H, Wardenaar R, Spierings DCJ, Spencer C, Schmitt AM, Tippu Z, Lingard K, Grostate L, Peat K, Kelly K, Sarker S, Vaughan S, Mangwende M, Terry L, Kelly D, Biano J, Murra A, Korteweg J, Lewis C, O'Flaherty M, Cattin AL, Emmerich M, Gerard CL, Pallikonda HA, Lynch J, Mason R, Rogiers A, Xu H, Huebner A, McGranahan N, Al Bakir M, Murai J, Naceur-Lombardelli C, Borg E, Mitchison M, Moore DA, Falzon M, Proctor I, Stamp GWH, Nye EL, Young K, Furness AJS, Pickering L, Stewart R, Mahadeva U, Green A, Larkin J, Litchfield K, Swanton C, Jamal-Hanjani M, and Turajlic S

Subjects
Humans, Mutation, Evolution, Molecular, DNA, Melanoma pathology, Brain Neoplasms
Abstract

Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma., Significance: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA. See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275., (©2023 The Authors; Published by the American Association for Cancer Research.)

Published
2023
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6. Sotrovimab restores neutralization against current Omicron subvariants in patients with blood cancer.

Author

Wu MY, Shepherd STC, Fendler A, Carr EJ, Au L, Harvey R, Dowgier G, Hobbs A, Herman LS, Ragno M, Adams L, Schmitt AM, Tippu Z, Shum B, Farag S, Rogiers A, O'Reilly N, Bawumia P, Smith C, Carlyle E, Edmonds K, Del Rosario L, Lingard K, Mangwende M, Holt L, Ahmod H, Korteweg J, Foley T, Barber T, Hepworth S, Emslie-Henry A, Caulfield-Lynch N, Byrne F, Deng D, Williams B, Brown M, Caidan S, Gavrielides M, MacRae JI, Kelly G, Peat K, Kelly D, Murra A, Kelly K, O'Flaherty M, Popat S, Yousaf N, Jhanji S, Tatham K, Cunningham D, Van As N, Young K, Furness AJS, Pickering L, Beale R, Swanton C, Gandhi S, Gamblin S, Bauer DLV, Kassiotis G, Howell M, Walker S, Nicholson E, Larkin J, Wall EC, and Turajlic S

Subjects
Humans, SARS-CoV-2, COVID-19, Hematologic Neoplasms drug therapy, Neoplasms
Abstract

Wu et al. report that patients with hematologic malignancies have reduced immunity against SARS-CoV-2 Omicron subvariants and Sotrovimab retains neutralizing capacity against all tested Omicron subvariants., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Published
2023
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7. Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer.

Author

Fendler A, Shepherd STC, Au L, Wu M, Harvey R, Wilkinson KA, Schmitt AM, Tippu Z, Shum B, Farag S, Rogiers A, Carlyle E, Edmonds K, Del Rosario L, Lingard K, Mangwende M, Holt L, Ahmod H, Korteweg J, Foley T, Barber T, Emslie-Henry A, Caulfield-Lynch N, Byrne F, Deng D, Kjaer S, Song OR, Queval CJ, Kavanagh C, Wall EC, Carr EJ, Caidan S, Gavrielides M, MacRae JI, Kelly G, Peat K, Kelly D, Murra A, Kelly K, O'Flaherty M, Shea RL, Gardner G, Murray D, Popat S, Yousaf N, Jhanji S, Tatham K, Cunningham D, Van As N, Young K, Furness AJS, Pickering L, Beale R, Swanton C, Gandhi S, Gamblin S, Bauer DLV, Kassiotis G, Howell M, Nicholson E, Walker S, Wilkinson RJ, Larkin J, and Turajlic S

Subjects
Humans, Antibodies, Neutralizing, Antibodies, Viral, BNT162 Vaccine, Clinical Studies as Topic, Immunity, SARS-CoV-2, COVID-19 prevention & control, COVID-19 Vaccines immunology, Neoplasms
Abstract

Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titers and T cell responses after the fourth vaccine dose increased compared with that after the third vaccine dose. Patients who received B cell-depleting therapies within the 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination., Competing Interests: Declaration of interests The authors declare no competing interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Published
2022
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8. Omicron neutralising antibodies after third COVID-19 vaccine dose in patients with cancer.

Author

Fendler A, Shepherd STC, Au L, Wu M, Harvey R, Schmitt AM, Tippu Z, Shum B, Farag S, Rogiers A, Carlyle E, Edmonds K, Del Rosario L, Lingard K, Mangwende M, Holt L, Ahmod H, Korteweg J, Foley T, Barber T, Emslie-Henry A, Caulfield-Lynch N, Byrne F, Deng D, Kjaer S, Song OR, Queval C, Kavanagh C, Wall EC, Carr EJ, Caidan S, Gavrielides M, MacRae JI, Kelly G, Peat K, Kelly D, Murra A, Kelly K, O'Flaherty M, Shea RL, Gardner G, Murray D, Yousaf N, Jhanji S, Tatham K, Cunningham D, Van As N, Young K, Furness AJS, Pickering L, Beale R, Swanton C, Gandhi S, Gamblin S, Bauer DLV, Kassiotis G, Howell M, Nicholson E, Walker S, Larkin J, and Turajlic S

Subjects
Antibodies, Neutralizing immunology, Antibodies, Viral immunology, COVID-19 Vaccines, Humans, SARS-CoV-2, COVID-19 prevention & control, Neoplasms
Abstract

Competing Interests: DC has received institutional grant funding from MedImmune/AstraZeneca, Clovis, Eli Lilly, 4SC, Bayer, Celgene, Leap, Roche. DLVB has received grant funding from AstraZeneca. CS is funded by CRUK (TRACERx, PEACE and CRUK Cancer Immunotherapy Catalyst Network), the CRUK Lung Cancer Centre of Excellence (C11496/A30025), the Rosetrees Trust, Butterfield and Stoneygate Trusts, the Novo Nordisk Foundation (ID16584), a Royal Society Professorship Enhancement award (RP/EA/180007), the National Institute of Health Research (NIHR) Biomedical Research Centre at University College London Hospitals, the CRUK University College London Centre, the Experimental Cancer Medicine Centre and the Breast Cancer Research Foundation (BCRF 20-157). This work was supported by a Stand Up To Cancer‐LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational research grant (SU2C-AACR-DT23-17 to SMD and AES). Stand Up To Cancer is a division of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the scientific partner of SU2C. CS received an ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union's Horizon 2020 research and innovation programme (835297). CS is a Royal Society Napier Research Professor (RP150154). ST is funded by Cancer Research UK (A29911); the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC10988), the UK Medical Research Council (FC10988), and the Wellcome Trust (FC10988); the NIHR Biomedical Research Centre at the Royal Marsden Hospital and Institute of Cancer Research (grant reference number A109), the Royal Marsden Cancer Charity, The Rosetrees Trust (A2204), Ventana Medical Systems (grant reference numbers 10467 and 10530), the National Institute of Health (U01 CA247439) and Melanoma Research Alliance (686061). ST has received speaking fees from Roche, Astra Zeneca, Novartis, and Ipsen. ST has the following patents filed: Indel mutations as a therapeutic target and predictive biomarker PCTGB2018/051892 PCTGB2018/051893 and Clear Cell Renal Cell Carcinoma Biomarkers P113326GB. All other authors declare no competing interests. AF, STCS, LA, MW, and RH contributed equally.

Published
2022
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9. Functional antibody and T cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study.

Author

Fendler A, Au L, Shepherd STC, Byrne F, Cerrone M, Boos LA, Rzeniewicz K, Gordon W, Shum B, Gerard CL, Ward B, Xie W, Schmitt AM, Joharatnam-Hogan N, Cornish GH, Pule M, Mekkaoui L, Ng KW, Carlyle E, Edmonds K, Rosario LD, Sarker S, Lingard K, Mangwende M, Holt L, Ahmod H, Stone R, Gomes C, Flynn HR, Agua-Doce A, Hobson P, Caidan S, Howell M, Wu M, Goldstone R, Crawford M, Cubitt L, Patel H, Gavrielides M, Nye E, Snijders AP, MacRae JI, Nicod J, Gronthoud F, Shea RL, Messiou C, Cunningham D, Chau I, Starling N, Turner N, Welsh L, van As N, Jones RL, Droney J, Banerjee S, Tatham KC, Jhanji S, O'Brien M, Curtis O, Harrington K, Bhide S, Bazin J, Robinson A, Stephenson C, Slattery T, Khan Y, Tippu Z, Leslie I, Gennatas S, Okines A, Reid A, Young K, Furness AJS, Pickering L, Gandhi S, Gamblin S, Swanton C, Nicholson E, Kumar S, Yousaf N, Wilkinson KA, Swerdlow A, Harvey R, Kassiotis G, Larkin J, Wilkinson RJ, and Turajlic S

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Neutralizing immunology, Antibodies, Viral immunology, COVID-19 blood, COVID-19 mortality, Female, Follow-Up Studies, Humans, Immunity, Cellular, Male, Middle Aged, Neoplasms blood, Neoplasms immunology, Prospective Studies, SARS-CoV-2 immunology, Spike Glycoprotein, Coronavirus immunology, Young Adult, Antibodies, Neutralizing blood, Antibodies, Viral blood, COVID-19 immunology, Neoplasms complications, T-Lymphocytes immunology
Abstract

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4 + responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer., (© 2021. The Author(s).)

Published
2021
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10. Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study.

Author

Fendler A, Shepherd STC, Au L, Wilkinson KA, Wu M, Byrne F, Cerrone M, Schmitt AM, Joharatnam-Hogan N, Shum B, Tippu Z, Rzeniewicz K, Boos LA, Harvey R, Carlyle E, Edmonds K, Del Rosario L, Sarker S, Lingard K, Mangwende M, Holt L, Ahmod H, Korteweg J, Foley T, Bazin J, Gordon W, Barber T, Emslie-Henry A, Xie W, Gerard CL, Deng D, Wall EC, Agua-Doce A, Namjou S, Caidan S, Gavrielides M, MacRae JI, Kelly G, Peat K, Kelly D, Murra A, Kelly K, O'Flaherty M, Dowdie L, Ash N, Gronthoud F, Shea RL, Gardner G, Murray D, Kinnaird F, Cui W, Pascual J, Rodney S, Mencel J, Curtis O, Stephenson C, Robinson A, Oza B, Farag S, Leslie I, Rogiers A, Iyengar S, Ethell M, Messiou C, Cunningham D, Chau I, Starling N, Turner N, Welsh L, van As N, Jones RL, Droney J, Banerjee S, Tatham KC, O'Brien M, Harrington K, Bhide S, Okines A, Reid A, Young K, Furness AJS, Pickering L, Swanton C, Gandhi S, Gamblin S, Bauer DLV, Kassiotis G, Kumar S, Yousaf N, Jhanji S, Nicholson E, Howell M, Walker S, Wilkinson RJ, Larkin J, and Turajlic S

Subjects
Aged, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Antibodies, Viral blood, Antibodies, Viral immunology, BNT162 Vaccine administration & dosage, COVID-19 blood, COVID-19 immunology, ChAdOx1 nCoV-19 administration & dosage, Female, Humans, Immunity, Cellular, Immunogenicity, Vaccine, Male, Middle Aged, Neoplasms blood, Neoplasms complications, Prospective Studies, T-Lymphocytes immunology, BNT162 Vaccine immunology, COVID-19 prevention & control, ChAdOx1 nCoV-19 immunology, Neoplasms immunology, SARS-CoV-2 immunology
Abstract

Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) ( NCT03226886 ) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic., (© 2021. The Author(s).)

Published
2021
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11. Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma.

Author

Au L, Hatipoglu E, Robert de Massy M, Litchfield K, Beattie G, Rowan A, Schnidrig D, Thompson R, Byrne F, Horswell S, Fotiadis N, Hazell S, Nicol D, Shepherd STC, Fendler A, Mason R, Del Rosario L, Edmonds K, Lingard K, Sarker S, Mangwende M, Carlyle E, Attig J, Joshi K, Uddin I, Becker PD, Sunderland MW, Akarca A, Puccio I, Yang WW, Lund T, Dhillon K, Vasquez MD, Ghorani E, Xu H, Spencer C, López JI, Green A, Mahadeva U, Borg E, Mitchison M, Moore DA, Proctor I, Falzon M, Pickering L, Furness AJS, Reading JL, Salgado R, Marafioti T, Jamal-Hanjani M, Kassiotis G, Chain B, Larkin J, Swanton C, Quezada SA, and Turajlic S

Subjects
CD8-Positive T-Lymphocytes, Carcinoma, Renal Cell genetics, Clinical Trials, Phase II as Topic, Endogenous Retroviruses genetics, Gene Expression Profiling methods, Genomics methods, Humans, Immune Checkpoint Inhibitors pharmacology, Kidney Neoplasms genetics, Nivolumab pharmacology, Prospective Studies, Sequence Analysis, RNA, Single-Cell Analysis, Tumor Escape, Tumor Microenvironment, Exome Sequencing, Carcinoma, Renal Cell drug therapy, Drug Resistance, Neoplasm, Immune Checkpoint Inhibitors administration & dosage, Kidney Neoplasms drug therapy, Nivolumab administration & dosage, Receptors, Antigen, T-Cell genetics
Abstract

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8 + T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action., Competing Interests: Declaration of interests L.A. is funded by the Royal Marsden Cancer Charity. E.H. and M.M. are funded by Cancer Research UK (CRUK). F.B. is funded by the Rosetrees Trust (M829). J.A. is a full-time employee of Hoffmann-La Roche AG (Basel, Switzerland). D.A.M has received consultancy fees from AstraZeneca, Thermo Fisher, and Eli Lilly. A.F. has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 892360. L.P. has received research funding from Pierre Fabre, and honoraria from Pfizer, Ipsen, Bristol-Myers Squibb, and EUSA Pharma. R.S. has received non-financial support from Merck and Bristol Myers Squibb; research support from Merck, Puma Biotechnology, and Roche; and advisory board fees for Bristol Myers Squibb; and personal fees from Roche for an advisory board related to a trial-research project; all related to breast cancer research projects. R.S. reports no conflict of interests related to this project. M.J.H. is a Cancer Research UK (CRUK) Clinician Scientist (RCCFEL\100099) and has received funding from CRUK, National Institute for Health Research, Rosetrees Trust, UKI NETs and NIHR University College London Hospitals Biomedical Research Center. M.J.H. is a member of the Scientific Advisory Board and Steering Committee for Achilles Therapeutics. G.K. is a scientific co-founder of and consulting for Enara Bio and a member of its scientific advisory board. G.K. receives core funding from the Francis Crick Institute (FC0010099). B.C. is supported by a CRUK Project Grant. J.L. has received research funding from Bristol-Myers Squibb, Merck, Novartis, Pfizer, Achilles Therapeutics, Roche, Nektar Therapeutics, Covance, Immunocore, Pharmacyclics, and Aveo, and served as a consultant to Achilles, AstraZeneca, Boston Biomedical, Bristol-Myers Squibb, Eisai, EUSA Pharma, GlaxoSmithKline, Ipsen, Imugene, Incyte, iOnctura, Kymab, Merck Serono, Nektar, Novartis, Pierre Fabre, Pfizer, Roche Genentech, Secarna, and Vitaccess. C.S. acknowledges grant support from Pfizer, AstraZeneca, Bristol-Myers Squibb, Roche-Ventana, Boehringer-Ingelheim, Archer Dx Inc (collaboration in minimal residual disease sequencing technologies), and Ono Pharmaceutical, is an AstraZeneca Advisory Board member and Chief Investigator for the MeRmaiD1 clinical trial, has consulted for Pfizer, Novartis, GlaxoSmithKline, MSD, Bristol-Myers Squibb, Celgene, AstraZeneca, Illumina, Genentech, Roche-Ventana, GRAIL, Medicxi, Bicycle Therapeutics, and the Sarah Cannon Research Institute, has stock options in Apogen Biotechnologies, Epic Bioscience, GRAIL, and has stock options and is co-founder of Achilles Therapeutics. Patents: C.S. holds European patents relating to assay technology to detect tumor recurrence (PCT/GB2017/053289); to targeting neoantigens (PCT/EP2016/059401), identifying patent response to immune checkpoint blockade (PCT/EP2016/071471), determining HLA LOH (PCT/GB2018/052004), predicting survival rates of patients with cancer (PCT/GB2020/050221), identifying patients who respond to cancer treatment (PCT/GB2018/051912), a US patent relating to detecting tumor mutations (PCT/US2017/28013) and both a European and US patent related to identifying insertion/deletion mutation targets (PCT/GB2018/051892). C.S. is Royal Society Napier Research Professor (RP150154). His work is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001169), the UK Medical Research Council (FC001169), and the Wellcome Trust (FC001169). C.S. is funded by Cancer Research UK (TRACERx, PEACE and CRUK Cancer Immunotherapy Catalyst Network), Cancer Research UK Lung Cancer Center of Excellence, the Rosetrees Trust, Butterfield and Stoneygate Trusts, NovoNordisk Foundation (ID16584), Royal Society Research Professorship Enhancement Award (RP/EA/180007), the NIHR BRC at University College London Hospitals, the CRUK-UCL Center, Experimental Cancer Medicine Center and the Breast Cancer Research Foundation, USA (BCRF). His research is supported by a Stand Up To Cancer-LUNGevity-American Lung Association Lung Cancer Interception Dream Team Translational Research Grant (SU2C-AACR-DT23-17). Stand Up To Cancer is a program of the Entertainment Industry Foundation. Research grants are administered by the American Association for Cancer Research, the Scientific Partner of SU2C. C.S. also receives funding from the European Research Council (ERC) under the European Union’s Seventh Framework Program (FP7/2007-2013) Consolidator Grant (FP7-THESEUS-617844), European Commission ITN (FP7-PloidyNet 607722), an ERC Advanced Grant (PROTEUS) from the European Research Council under the European Union’s Horizon 2020 research and innovation program (835297), and Chromavision from the European Union’s Horizon 2020 research and innovation program (665233). S.A.Q. is a CRUK Senior Cancer Research Fellowship (C36463/A22246) and is funded by a CRUK Biotherapeutic Program Grant (C36463/A20764) and the Rosetrees and Stonygate Trusts (A1388) and a donation from the Khoo Teck Puat UK Foundation via the UCL Cancer Institute Research Trust (539288). S.T. is funded by Cancer Research UK (grant reference number C50947/A18176), the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC0010988), the UK Medical Research Council (FC0010988), and the Wellcome Trust (FC0010988), the National Institute for Health Research (NIHR) Biomedical Research Center at the Royal Marsden Hospital and Institute of Cancer Research (grant reference number A109), the Royal Marsden Cancer Charity, The Rosetrees Trust (grant reference number A2204), Ventana Medical Systems Inc (grant reference numbers 10467 and 10530), the National Institutes of Health (Bethesda, MD) and Melanoma Research Alliance. ST has received speaking fees from Roche, Astra Zeneca, Novartis, and Ipsen. S.T. has the following patents filed: Indel mutations as a therapeutic target and predictive biomarker PCTGB2018/051892 and PCTGB2018/051893 and Clear Cell Renal Cell Carcinoma Biomarkers P113326GB., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2021
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