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Your search keyword '"Coussens, L. M."' showing total 5 results
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5 results on '"Coussens, L. M."'

1. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients

Author

Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., Prieto, P. A., Vicente, D., Hoffman, K., Wei, S. C., Cogdill, A. P., Zhao, L., Hudgens, C. W., Hutchinson, D. S., Manzo, T., de Macedo, M. Petaccia, Cotechini, T., Kumar, T., Chen, W. S., Reddy, S. M., Sloane, R. Szczepaniak, Galloway-Pena, J., Jiang, H., Chen, P. L., Shpall, E. J., Rezvani, K., Alousi, A. M., Chemaly, R. F., Shelburne, S., Vence, L. M., Okhuysen, P. C., Jensen, V. B., Swennes, A. G., McAllister, F., Sanchez, E. Marcelo Riquelme, Zhang, Y., Le Chatelier, E., Zitvogel, L., Pons, N., Austin-Breneman, J. L., Haydu, L. E., Burton, E. M., Gardner, J. M., Sirmans, E., Hu, J., Lazar, A. J., Tsujikawa, T., Diab, A., Tawbi, H., Glitza, I. C., Hwu, W. J., Patel, S. P., Woodman, S. E., Amaria, R. N., Davies, M. A., Gershenwald, J. E., Hwu, P., Lee, J. E., Zhang, J., Coussens, L. M., Cooper, Z. A., Futreal, P. A., Daniel, C. R., Ajami, N. J., Petrosino, J. F., Tetzlaff, M. T., Sharma, P., Allison, J. P., Jenq, R. R., and Wargo, J. A.

Published
2018

2. Ibrutinib in combination with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic pancreatic adenocarcinoma: phase III RESOLVE study

Author

Tempero, M., Oh, D-Y, Tabernero, J., Reni, M., Van Cutsem, E., Hendifar, A., Waldschmidt, D-T, Starling, N., Bachet, J-B, Chang, H-M, Maurel, J., Garcia-Carbonero, R., Lonardi, S., Coussens, L. M., Fong, L., Tsao, L. C., Cole, G., Jr., James, D., Macarulla, T., Tempero, M., Oh, D-Y, Tabernero, J., Reni, M., Van Cutsem, E., Hendifar, A., Waldschmidt, D-T, Starling, N., Bachet, J-B, Chang, H-M, Maurel, J., Garcia-Carbonero, R., Lonardi, S., Coussens, L. M., Fong, L., Tsao, L. C., Cole, G., Jr., James, D., and Macarulla, T.

Abstract

Background: First-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC) includes nab-paclitaxel/gemcitabine. Ibrutinib, a Bruton's tyrosine kinase inhibitor, exhibits antitumor activity through tumor microenvironment modulation. The safety and efficacy of first-line ibrutinib plus nab-paclitaxel/gemcitabine treatment in patients with PDAC were evaluated. Patients and methods: RESOLVE (NCT02436668) was a phase III, randomized, double-blind, placebo-controlled study. Patients (histologically-confirmed PDAC; stage IV diagnosis >6 weeks of randomization; Karnofsky performance score >70) were randomized to once-daily oral ibrutinib (560 mg) or placebo plus nab-paclitaxel (125 mg/m(2)) and gemcitabine (1000 mg/m(2)). Primary endpoints were overall survival (OS) and investigator-assessed progression-free survival (PFS); overall response rate and safety were assessed. Results: In total, 424 patients were randomized (ibrutinib arm, n = 211; placebo arm, n = 213). Baseline characteristics were balanced across arms. After a median follow-up of 25 months, there was no significant difference in OS between ibrutinib plus nab-paclitaxel/gemcitabine versus placebo plus nab-paclitaxel/gemcitabine (median of 9.7 versus 10.8 months; P = 0.3225). PFS was shorter for ibrutinib plus nab-paclitaxel/gemcitabine compared with placebo plus nab-paclitaxel/gemcitabine (median 5.3 versus 6.0 months; P < 0.0001). Overall response rates were 29% and 42%, respectively (P = 0.0058). Patients in the ibrutinib arm had less time on treatment and received lower cumulative doses for all agents compared with the placebo arm. The most common grade >3 adverse events for ibrutinib versus placebo arms included neutropenia (24% versus 35%), peripheral sensory neuropathy (17% versus 8%), and anemia (16% versus 17%). Primary reasons for any treatment discontinuation were disease progression and adverse events. Conclusions: Ibrutinib plus nab-paclitaxel/gemcitabine did not improve OS or PFS for pa

Published
2021

3. Composition, spatial characteristics, and prognostic significance of myeloid cell infiltration in pancreatic cancer

Author

Väyrynen, S. A. (Sara A.), Zhang, J. (Jinming), Yuan, C. (Chen), Väyrynen, J. P. (Juha P.), Dias Costa, A. (Andressa), Williams, H. (Hannah), Morales-Oyarvide, V. (Vicente), Lau, M. C. (Mai Chan), Rubinson, D. A. (Douglas A.), Dunne, R. F. (Richard F.), Kozak, M. M. (Margaret M.), Wang, W. (Wenjia), Agostini-Vulaj, D. (Diana), Drage, M. G. (Michael G.), Brais, L. (Lauren), Reilly, E. (Emma), Rahma, O. (Osama), Clancy, T. (Thomas), Wang, J. (Jiping), Linehan, D. C. (David C.), Aguirre, A. J. (Andrew J.), Fuchs, C. S. (Charles, S.), Coussens, L. M. (Lisa M.), Chang, D. T. (Daniel T.), Koong, A. C. (Albert C.), Hezel, A. F. (Aram F.), Ogino, S. (Shuji), Nowak, J. A. (Jonathan A.), Wolpin, B. M. (Brian M.), Väyrynen, S. A. (Sara A.), Zhang, J. (Jinming), Yuan, C. (Chen), Väyrynen, J. P. (Juha P.), Dias Costa, A. (Andressa), Williams, H. (Hannah), Morales-Oyarvide, V. (Vicente), Lau, M. C. (Mai Chan), Rubinson, D. A. (Douglas A.), Dunne, R. F. (Richard F.), Kozak, M. M. (Margaret M.), Wang, W. (Wenjia), Agostini-Vulaj, D. (Diana), Drage, M. G. (Michael G.), Brais, L. (Lauren), Reilly, E. (Emma), Rahma, O. (Osama), Clancy, T. (Thomas), Wang, J. (Jiping), Linehan, D. C. (David C.), Aguirre, A. J. (Andrew J.), Fuchs, C. S. (Charles, S.), Coussens, L. M. (Lisa M.), Chang, D. T. (Daniel T.), Koong, A. C. (Albert C.), Hezel, A. F. (Aram F.), Ogino, S. (Shuji), Nowak, J. A. (Jonathan A.), and Wolpin, B. M. (Brian M.)

Abstract

Purpose: Although abundant myeloid cell populations in the pancreatic ductal adenocarcinoma (PDAC) microenvironment have been postulated to suppress antitumor immunity, the composition of these populations, their spatial locations, and how they relate to patient outcomes are poorly understood. Experimental Design: To generate spatially resolved tumor and immune cell data at single-cell resolution, we developed two quantitative multiplex immunofluorescence assays to interrogate myeloid cells (CD15, CD14, ARG1, CD33, HLA-DR) and macrophages [CD68, CD163, CD86, IFN regulatory factor 5, MRC1 (CD206)] in the PDAC tumor microenvironment. Spatial point pattern analyses were conducted to assess the degree of colocalization between tumor cells and immune cells. Multivariable-adjusted Cox proportional hazards regression was used to assess associations with patient outcomes. Results: In a multi-institutional cohort of 305 primary PDAC resection specimens, myeloid cells were abundant, enriched within stromal regions, highly heterogeneous across tumors, and differed by somatic genotype. High densities of CD15⁺ARG1⁺ immunosuppressive granulocytic cells and M2-polarized macrophages were associated with worse patient survival. Moreover, beyond cell density, closer proximity of M2-polarized macrophages to tumor cells was strongly associated with disease-free survival, revealing the clinical significance and biologic importance of immune cell localization within tumor areas. Conclusions: A diverse set of myeloid cells are present within the PDAC tumor microenvironment and are distributed heterogeneously across patient tumors. Not only the densities but also the spatial locations of myeloid immune cells are associated with patient outcomes, highlighting the potential role of spatially resolved myeloid cell subtypes as quantitative biomarkers for PDAC prognosis and therapy.

Published
2021

4. Correction to: Toward a comprehensive view of cancer immune responsiveness: A synopsis from the SITC workshop (Journal for ImmunoTherapy of Cancer (2020) 7 (131) DOI: 10.1186/s40425-019-0602-4)

Author

Bedognetti, D., Ceccarelli, M., Galluzzi, L., Lu, R., Palucka, K., Samayoa, J., Spranger, S., Warren, S., Wong, K. -K., Ziv, E., Chowell, D., Coussens, L. M., De Carvalho, D. D., Denardo, D. G., Galon, J., Kaufman, H. L., Kirchhoff, T., Lotze, M. T., Luke, J. J., Minn, A. J., Politi, K., Shultz, L. D., Simon, R., Thorsson, V., Weidhaas, J. B., Ascierto, M. L., Ascierto, P. A., Barnes, J. M., Barsan, V., Bommareddy, P. K., Bot, A., Church, S. E., Ciliberto, G., De Maria, A., Draganov, D., W. S., Ho, Mcgee, H. M., Monette, A., Murphy, J. F., Nistico, P., Park, W., Patel, M., Quigley, M., Radvanyi, L., Raftopoulos, H., Rudqvist, N. -P., Snyder, A., Sweis, R. F., Valpione, S., Zappasodi, R., Butterfield, L. H., Disis, M. L., Fox, B. A., Cesano, A., and Marincola, F. M.

Published
2019

5. Ibrutinib in combination with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic pancreatic adenocarcinoma: phase III RESOLVE study.

Author

Tempero M, Oh DY, Tabernero J, Reni M, Van Cutsem E, Hendifar A, Waldschmidt DT, Starling N, Bachet JB, Chang HM, Maurel J, Garcia-Carbonero R, Lonardi S, Coussens LM, Fong L, Tsao LC, Cole G Jr, James D, and Macarulla T

Subjects
Adenine analogs & derivatives, Albumins adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Deoxycytidine analogs & derivatives, Humans, Paclitaxel adverse effects, Piperidines, Treatment Outcome, Tumor Microenvironment, Gemcitabine, Adenocarcinoma drug therapy, Pancreatic Neoplasms drug therapy
Abstract

Background: First-line treatment of metastatic pancreatic ductal adenocarcinoma (PDAC) includes nab-paclitaxel/gemcitabine. Ibrutinib, a Bruton's tyrosine kinase inhibitor, exhibits antitumor activity through tumor microenvironment modulation. The safety and efficacy of first-line ibrutinib plus nab-paclitaxel/gemcitabine treatment in patients with PDAC were evaluated., Patients and Methods: RESOLVE (NCT02436668) was a phase III, randomized, double-blind, placebo-controlled study. Patients (histologically-confirmed PDAC; stage IV diagnosis ≥6 weeks of randomization; Karnofsky performance score ≥70) were randomized to once-daily oral ibrutinib (560 mg) or placebo plus nab-paclitaxel (125 mg/m 2 ) and gemcitabine (1000 mg/m 2 ). Primary endpoints were overall survival (OS) and investigator-assessed progression-free survival (PFS); overall response rate and safety were assessed., Results: In total, 424 patients were randomized (ibrutinib arm, n = 211; placebo arm, n = 213). Baseline characteristics were balanced across arms. After a median follow-up of 25 months, there was no significant difference in OS between ibrutinib plus nab-paclitaxel/gemcitabine versus placebo plus nab-paclitaxel/gemcitabine (median of 9.7 versus 10.8 months; P = 0.3225). PFS was shorter for ibrutinib plus nab-paclitaxel/gemcitabine compared with placebo plus nab-paclitaxel/gemcitabine (median 5.3 versus 6.0 months; P < 0.0001). Overall response rates were 29% and 42%, respectively (P = 0.0058). Patients in the ibrutinib arm had less time on treatment and received lower cumulative doses for all agents compared with the placebo arm. The most common grade ≥3 adverse events for ibrutinib versus placebo arms included neutropenia (24% versus 35%), peripheral sensory neuropathy (17% versus 8%), and anemia (16% versus 17%). Primary reasons for any treatment discontinuation were disease progression and adverse events., Conclusions: Ibrutinib plus nab-paclitaxel/gemcitabine did not improve OS or PFS for patients with PDAC. Safety was consistent with known profiles for these agents., Competing Interests: Disclosure MT: consultancy/advisory role with Advance Medical, AstraZeneca, Bristol-Myers Squibb (BMS), EcoR1 Capital, Elicio Therapeutics, FibroGen, Inc., GlaxoSmithKline, Immunovia, ISPEN, Karyopharm Therapeutics, Merck & Co., Inc., and Swedish Orphan Biovitrum; research funding from Celgene and Halozyme; other relationship(s) with Astellas Pharma Global Development, Inc. (DSMC). D-YO: consultancy/advisory role with ASLAN, AstraZeneca, Bayer, Genentech/Roche, Halozyme, Merck Serono, Novartis, Taiho, and Zymeworks; research funding from Array, AstraZeneca, and Eli Lilly. JT: consultancy/advisory role with Array Biopharma, AstraZeneca, Bayer, BeiGene, Biocartis, Boehringer Ingelheim, Chugai, F. Hoffmann-La Roche Ltd, Foundation Medicine, Genentech, Inc., Genmab A/S, HalioDX SAS, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, Merck Sharp & Dohme (MSD), Menarini, Merck Serono, Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics LLC, an AbbVie Company, ProteoDesign SL, Rafael Pharmaceuticals, Roche Diagnostics, Sanofi, Seagen, Seattle Genetics, Servier, Symphogen, Taiho, and VCN Biosciences. MR: honoraria from Baxalta, Celgene, and Shire; consultancy/advisory role with Baxalta, Celgene, Eli Lilly, Novartis, Novocure, Pfizer, and Shire; research funding to Institution from Celgene; travel expenses from Celgene, AstraZeneca; other relationship(s) with AstraZeneca, Boston Pharmaceuticals, and Celgene. EVC: consultancy/advisory role with AstraZeneca, Bayer, BMS, Celgene, Lilly, MSD, Merck DGaA, Novartis, Roche, and Servier; research funding from Amgen, Bayer, Boehringer Ingelheim, BMS, Celgene, Ipsen, Lilly, Merck, Merck KGaA, Novartis, Roche, and Servier. AH: consultancy/advisory role with AbbVie, Ipsen, Merck, and Novartis; research funding from Ipsen. D-TW: speakers' bureau for AstraZeneca, BMS, Celgene, Eisai, Falk, Ipsen, Novartis, Roche, Servier, Shire Baxalta, and Sirtex; travel expenses from Bayer Health Pharma, Celgene, Ipsen, Novartis, and Sirtex. NS: honoraria from Eli Lilly, Merck Serono, MSD Oncology, and Pierre Fabre; consultancy/advisory role with AstraZeneca, Pfizer, and Servier; research funding from AstraZeneca, BMS, and Pfizer; travel expenses from AstraZeneca, BMS, Eli Lilly, Merck, and Roche. J-BB: honoraria from Amgen, AstraZeneca, Bayer, Celgene, Merck Serono, Mundipharma, Pierre Fabre, Roche, Sanofi, and Servier; consultancy/advisory role with Amgen, AstraZeneca, Bayer, Merck Serono, Pierre Fabre, and Servier; travel expenses from Amgen, Bayer, Celgene, Merck Serono, Roche, Sanofi, and Servier. H-MC: research funding from Astellas, Halozyme, Pharmacyclics LLC, an AbbVie Company, Senhwa Biosciences, Taiho Oncology. JM: consultancy/advisory role with Advance Medical, AstraZeneca, Bayer, Pierre-Fabre, Roche, Sanofi, Servier, Shire, and Sirtex; research funding from Amgen, Biocartis, Incyte, Merck, Nanostring, and Servier; patents, royalties, or other intellectual property with GAIS-42-patent P5020EP00. RG: honoraria from AAA, Amgen, Bayer, BMS, Ipsen, Lilly, Merck, MSD, Novartis, PharmaMar, Pfizer, Roche, and Sanofi; research funding from ARMO Biosciences, AstraZeneca, Pfizer, Novartis, Ipsen, Roche, Pharmacyclics LLC, an AbbVie Company, Boston Biomedicals, Merck, MSD, Amgen, Sanofi, Bayer, BMS, Boehringer, Sysmex, Gilead Sciences, Servier, Adacap, VCN, Lilly, PharmaMar; travel expenses from Ipsen, Merck, Novartis, and Servier. SL: consultancy/advisory role with Amgen, Lilly, Merck Serono, and Servier; research funding from Amgen and Merck Serono; speakers' bureau for BMS, Lilly, Merck Serono, Roche, and Servier. LMC: employment with Oregon Health & Science University; honoraria from Aduro Biotech, AstraZeneca, Carisma Therapeutics, Inc., Cell Signaling Technologies, CytomX Therapeutics, Inc., Jackson Laboratories, Seattle Genetics, Syndax Pharmaceuticals, Inc., Verseau Therapeutics, Inc., and Zymeworks, Inc.; consultancy/advisory role with Carisma Therapeutics Inc., Cell Signaling Technologies, CytomX Therapeutics, Inc., Syndax Pharmaceuticals, Inc., Verseau Therapeutics, Inc., and Zymeworks, Inc.; research funding (for profit) Acerta Pharma, Deciphera Pharmaceuticals, Innate Pharma, Roche Glycart and Parker Institute for Immunotherapy, and Syndax Pharmaceuticals, Inc.; patents, royalties, or other intellectual property with Oregon Health & Science University; other relationship(s) with Reagent from Reagent support from: Acerta Pharma, LLC, Cell Signaling Technologies, Deciphera Pharmaceuticals, Genentech/Roche Glycart AG, NanoString Technologies, Inc., Plexxikon, Inc, and Syndax Pharmaceuticals. LF: research funding from AbbVie, Bavarian Nordic, BMS, Dendreon, Janssen, Merck, Roche/Genentech. GC: employment with Pharmacyclics LLC, an AbbVie Company; stock ownership in AbbVie. DJ: employment with Pharmacyclics LLC, an AbbVie Company; leadership role with Pharmacyclics LLC, an AbbVie Company; stock ownership in AbbVie; patents, royalties, or other intellectual property with Pharmacyclics LLC, an AbbVie Company. TM: consultancy/advisory role with Advance Medical HCMS, Baxter, BioLineRX Ltd, Celgene SLU, Eisai, Genzyme, Incyte, IPSEN Pharma Lab. Menarini, Lab. Servier, Lilly, QED Therapeutics, MSD, Prime Oncology EU, QED Therapeutics Inc., Sanofi-Aventis; research funding from Agios, ASLAN, AstraZeneca, Bayer, Celgene, Genentech, Hallozyme, Immunomedics, Lilly, Merimarck, Millenium, Novartis, Pfizer, Pharmacyclics LLC, an AbbVie Company, and Roche; travel expenses from Servier and Incyte. LCT has declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2021
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