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6. Immune Cell Distributions in the Blood of Healthy Individuals at High Genetic Risk of Parkinson's Disease.

Author

Deecke, Laura, Goldeck, David, Ohlei, Olena, Homann, Jan, Demuth, Ilja, Bertram, Lars, Pawelec, Graham, and Lill, Christina M.

Abstract

The immune system likely plays a key role in Parkinson's disease (PD) pathophysiology. Thus, we investigated whether immune cell compositions are already altered in healthy individuals at high genetic risk for PD. We quantified 92 immune cell subtypes in the blood of 442 individuals using multicolor flow cytometry. Polygenic risk scores (PGS) for PD were calculated based on genome-wide significant SNPs (n = 87) from a large genome-wide association study (n = 1,530,403). Linear regression analyses did not reveal significant associations between PGS and any immune cell subtype (FDR = 0.05). Nominally significant associations were observed for NKG2C+ B cells (p = 0.026) in the overall sample. Older participants at increased genetic PD risk also showed a higher proportion of myeloid dendritic cells (p = 0.019) and CD27+CD4+ memory T cells (p = 0.043). Several immune cells were nominally statistically associated in women only. These findings suggest that major alterations of immune cells only occur later in the progression of PD. [ABSTRACT FROM AUTHOR]

Published
2024
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11. The conundrum of human immune system “senescence”

Author

Pawelec, Graham, Bronikowski, Anne, Cunnane, Stephen C., Ferrucci, Luigi, Franceschi, Claudio, Fülöp, Tamas, Gaudreau, Pierrette, Gladyshev, Vadim N., Gonos, Efstathios S., Gorbunova, Vera, Kennedy, Brian K., Larbi, Anis, Lemaître, Jean-François, Liu, Guang-Hui, Maier, Andrea B., Morais, José A., Nóbrega, Otávio T., Moskalev, Alexey, Rikkert, Marcel Olde, Seluanov, Andrei, Senior, Alistair M., Ukraintseva, Svetlana, Vanhaelen, Quentin, Witkowski, Jacek, and Cohen, Alan A.

Published
2020
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12. Lack of consensus on an aging biology paradigm? A global survey reveals an agreement to disagree, and the need for an interdisciplinary framework

Author

Cohen, Alan A., Kennedy, Brian K., Anglas, Ulrich, Bronikowski, Anne M., Deelen, Joris, Dufour, Frédérik, Ferbeyre, Gerardo, Ferrucci, Luigi, Franceschi, Claudio, Frasca, Daniela, Friguet, Bertrand, Gaudreau, Pierrette, Gladyshev, Vadim N., Gonos, Efstathios S., Gorbunova, Vera, Gut, Philipp, Ivanchenko, Mikhail, Legault, Véronique, Lemaître, Jean-François, Liontis, Thomas, Liu, Guang-Hui, Liu, Mingxin, Maier, Andrea B., Nóbrega, Otávio T., Olde Rikkert, Marcel G.M., Pawelec, Graham, Rheault, Sylvie, Senior, Alistair M., Simm, Andreas, Soo, Sonja, Traa, Annika, Ukraintseva, Svetlana, Vanhaelen, Quentin, Van Raamsdonk, Jeremy M., Witkowski, Jacek M., Yashin, Anatoliy I., Ziman, Robert, and Fülöp, Tamàs

Published
2020
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13. To help aging populations, classify organismal senescence

Author

Calimport, Stuart R. G., Bentley, Barry L., Stewart, Claire E., Pawelec, Graham, Scuteri, Angelo, Vinciguerra, Manlio, Slack, Cathy, Chen, Danica, Harries, Lorna W., Marchant, Gary, Fleming, G. Alexander, Conboy, Michael, Antebi, Adam, Small, Gary W., Gil, Jesus, Lakatta, Edward G., Richardson, Arlan, Rosen, Clifford, Nikolich, Karoly, Wyss-Coray, Tony, Steinman, Lawrence, Montine, Thomas, de Magalhães, João Pedro, Campisi, Judith, and Church, George

Published
2019

28. A novel series of conferences tackling the hurdles confronting the translation of novel cancer immunotherapies

Author

Bot, Adrian, Ahn, Mark, Bosch, Marnix, Brockstedt, Dirk, Butterfield, Lisa H, Cornforth, Andrew, Harrop, Richard, Kast, W, Koya, Richard, Marincola, Francesco, Margolin, Kim, McCoy, Candice, Pawelec, Graham, Rothman, John, Ramirez-Montagut, Teresa, Schlom, Jeffrey, Srivastava, Pramod, Wallis, Sarah, Walter, Steffen, Wang, Ena, and Waslif, John

Abstract

Abstract While there has been significant progress in advancing novel immune therapies to the bedside, much more needs to be done to fully tap into the potential of the immune system. It has become increasingly clear that besides practical and operational challenges, the heterogeneity of cancer and the limited efficacy profile of current immunotherapy platforms are the two main hurdles. Nevertheless, the promising clinical data of several approaches point to a roadmap that carries the promise to significantly advance cancer immunotherapy. A new annual series sponsored by Arrowhead Publishers and Conferences aims at bringing together scientific and business leadership from academia and industry, to identify, share and discuss most current priorities in research and translation of novel immune interventions. This Editorial provides highlights of the first event held earlier this year and outlines the focus of the second meeting to be held in 2013 that will be dedicated to stem cells and immunotherapy.

Published
2012

29. Defining the Critical Hurdles in Cancer Immunotherapy

Author

Fox, Bernard A, Schendel, Dolores J, Butterfield, Lisa H, Aamdal, Steinar, Allison, James P, Ascierto, Paolo, Atkins, Michael B, Bartunkova, Jirina, Bergmann, Lothar, Berinstein, Neil, Bonorino, Cristina C, Borden, Ernest, Bramson, Jonathan L, Britten, Cedrik M, Cao, Xuetao, Carson, William E, Chang, Alfred E, Characiejus, Dainius, Choudhury, A Raja, Coukos, George, de Gruijl, Tanja, Dillman, Robert O, Dolstra, Harry, Dranoff, Glenn, Durrant, Lindy G, Finke, James H, Galon, Jerome, Gollob, Jared A, Gouttefangeas, Cécile, Grizzi, Fabio, Guida, Michele, Håkansson, Leif, Hege, Kristen, Herberman, Ronald B, Hodi, F Stephen, Hoos, Axel, Huber, Christoph, Hwu, Patrick, Imai, Kohzoh, Jaffee, Elizabeth M, Janetzki, Sylvia, June, Carl H, Kalinski, Pawel, Kaufman, Howard L, Kawakami, Koji, Kawakami, Yutaka, Keilholtz, Ulrich, Khleif, Samir N, Kiessling, Rolf, Kotlan, Beatrix, Kroemer, Guido, Lapointe, Rejean, Levitsky, Hyam I, Lotze, Michael T, Maccalli, Cristina, Maio, Michele, Marschner, Jens-Peter, Mastrangelo, Michael J, Masucci, Giuseppe, Melero, Ignacio, Melief, Cornelius, Murphy, William J, Nelson, Brad, Nicolini, Andrea, Nishimura, Michael I, Odunsi, Kunle, Ohashi, Pamela S, O'Donnell-Tormey, Jill, Old, Lloyd J, Ottensmeier, Christian, Papamichail, Michael, Parmiani, Giorgio, Pawelec, Graham, Proietti, Enrico, Qin, Shukui, Rees, Robert, Ribas, Antoni, Ridolfi, Ruggero, Ritter, Gerd, Rivoltini, Licia, Romero, Pedro J, Salem, Mohamed L, Scheper, Rik J, Seliger, Barbara, Sharma, Padmanee, Shiku, Hiroshi, Singh-Jasuja, Harpreet, Song, Wenru, Straten, Per, Tahara, Hideaki, Tian, Zhigang, van Der Burg, Sjoerd H, von Hoegen, Paul, Wang, Ena, Welters, Marij JP, Winter, Hauke, Withington, Tara, Wolchok, Jedd D, Xiao, Weihua, and Zitvogel, Laurence

Abstract

Abstract Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer.

Published
2011

30. Aging and chronic inflammation: highlights from a multidisciplinary workshop

Author

Saavedra, Danay, Añé-Kourí, Ana Laura, Barzilai, Nir, Caruso, Calogero, Cho, Kyung-Hyun, Fontana, Luigi, Franceschi, Claudio, Frasca, Daniela, Ledón, Nuris, Niedernhofer, Laura J., Pereira, Karla, Robbins, Paul D., Silva, Alexa, Suarez, Gisela M., Vanden Berghe, Wim, von Zglinicki, Thomas, Pawelec, Graham, Lage, Agustín, Saavedra, Danay, Añé-Kourí, Ana Laura, Barzilai, Nir, Caruso, Calogero, Cho, Kyung-Hyun, Fontana, Luigi, Franceschi, Claudio, Frasca, Daniela, Ledón, Nuri, Niedernhofer, Laura J, Pereira, Karla, Robbins, Paul D, Silva, Alexa, Suarez, Gisela M, Berghe, Wim Vanden, von Zglinicki, Thoma, Pawelec, Graham, and Lage, Agustín

Subjects
Settore MED/04 - Patologia Generale, Aging, Biomodulina T, Immunosenescence, Cell senescence, Senolytic, Human medicine, Chronic inflammation, SASP, Biology, Inflammaging, Metformin
Abstract

Aging is a gradual, continuous series of natural changes in biological, physiological, immunological, environmental, psychological, behavioral, and social processes. Aging entails changes in the immune system characterized by a decrease in thymic output of naïve lymphocytes, an accumulated chronic antigenic stress notably caused by chronic infections such as cytomegalovirus (CMV), and immune cell senescence with acquisition of an inflammatory senescence-associated secretory phenotype (SASP). For this reason, and due to the SASP originating from other tissues, aging is commonly accompanied by low-grade chronic inflammation, termed “inflammaging”. After decades of accumulating evidence regarding age-related processes and chronic inflammation, the domain now appears mature enough to allow an integrative reinterpretation of old data. Here, we provide an overview of the topics discussed in a recent workshop “Aging and Chronic Inflammation” to which many of the major players in the field contributed. We highlight advances in systematic measurement and interpretation of biological markers of aging, as well as their implications for human health and longevity and the interventions that can be envisaged to maintain or improve immune function in older people.

Published
2023

32. Peripheral CD8 effector-memory type 1 T-cells correlate with outcome in ipilimumab-treated stage IV melanoma patients

Author

Wistuba-Hamprecht, Kilian, Martens, Alexander, Heubach, Florian, Romano, Emanuela, Geukes Foppen, Marnix, Yuan, Jianda, Postow, Michael, Wong, Phillip, Mallardo, Domenico, Schilling, Bastian, Di Giacomo, Anna Maria, Khammari, Amir, Dreno, Brigitte, Maio, Michele, Schadendorf, Dirk, Ascierto, Paolo A., Wolchok, Jedd D., Blank, Christian U., Garbe, Claus, Pawelec, Graham, and Weide, Benjamin

Published
2017
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41. Proportions of blood-borne Vδ1+ and Vδ2+ T-cells are associated with overall survival of melanoma patients treated with ipilimumab

Author

Wistuba-Hamprecht, Kilian, Martens, Alexander, Haehnel, Karin, Geukes Foppen, Marnix, Yuan, Jianda, Postow, Michael A., Wong, Phillip, Romano, Emanuela, Khammari, Amir, Dreno, Brigitte, Capone, Mariaelena, Ascierto, Paolo A., Demuth, Ilja, Steinhagen-Thiessen, Elisabeth, Larbi, Anis, Schilling, Bastian, Schadendorf, Dirk, Wolchok, Jedd D., Blank, Christian U., Pawelec, Graham, Garbe, Claus, and Weide, Benjamin

Published
2016
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48. Frequencies of activated T cell populations increase in breast milk of HCMV-seropositive mothers during local HCMV reactivation.

Author

Lazar, Katrin, Pawelec, Graham, Goelz, Rangmar, Hamprecht, Klaus, and Wistuba-Hamprecht, Kilian

Subjects
BREAST milk, T cells, CELL populations, MOTHERS, BLOOD cells
Abstract

Background: Human cytomegalovirus (HCMV) can reactivate in the mammary gland during lactation and is shed into breast milk of nearly every HCMV-IgG-seropositive mother of a preterm infant. Dynamics of breast milk leukocytes during lactation, as well as blood leukocytes and the comparison between both in the context of HCMV reactivation is not well understood. Methods: Here, we present the BlooMil study that aimed at comparing changes of immune cells in blood and breast milk from HCMVseropositive- vs -seronegative mothers, collected at four time ranges up to two months post-partum. Viral load was monitored by qPCR and nested PCR. Multiparameter flow cytometry was used to identify leukocyte subsets. Results: CD3+ T cell frequencies were found to increase rapidly in HCMVseropositive mothers’ milk, while they remained unchanged in matched blood samples, and in both blood and breast milk of HCMV-seronegatives. The activation marker HLA-DR was more strongly expressed on CD4+ and CD8+ T cells in all breast milk samples than matched blood samples, but HCMV-seropositive mothers displayed a significant increase of HLA-DR+ CD4+ and HLA-DR+ CD8+ T cells during lactation. The CD4+/CD8+ T cell ratio was lower in breast milk of HCMV-seropositive mothers than in the blood. HCMV-specific CD8+ T cell frequencies (recognizing pp65 or IE1) were elevated in breast milk relative to blood, which might be due to clonal expansion of these cells during local HCMV reactivation. Breast milk contained very low frequencies of naïve T cells with no significant differences depending on serostatus. Conclusion: Taken together, we conclude that the distribution of breast milk leukocyte populations is different from blood leukocytes and may contribute to the decrease of breast milk viral load in the late phase of HCMV reactivation in the mammary gland. [ABSTRACT FROM AUTHOR]

Published
2024
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49. Designing a broad-spectrum integrative approach for cancer prevention and treatment

Author

Block, Keith I., Gyllenhaal, Charlotte, Lowe, Leroy, Amedei, Amedeo, Amin, A.R.M. Ruhul, Amin, Amr, Aquilano, Katia, Arbiser, Jack, Arreola, Alexandra, Arzumanyan, Alla, Ashraf, S. Salman, Azmi, Asfar S., Benencia, Fabian, Bhakta, Dipita, Bilsland, Alan, Bishayee, Anupam, Blain, Stacy W., Block, Penny B., Boosani, Chandra S., Carey, Thomas E., Carnero, Amancio, Carotenuto, Marianeve, Casey, Stephanie C., Chakrabarti, Mrinmay, Chaturvedi, Rupesh, Chen, Georgia Zhuo, Chen, Helen, Chen, Sophie, Chen, Yi Charlie, Choi, Beom K., Ciriolo, Maria Rosa, Coley, Helen M., Collins, Andrew R., Connell, Marisa, Crawford, Sarah, Curran, Colleen S., Dabrosin, Charlotta, Damia, Giovanna, Dasgupta, Santanu, DeBerardinis, Ralph J., Decker, William K., Dhawan, Punita, Diehl, Anna Mae E., Dong, Jin-Tang, Dou, Q. Ping, Drew, Janice E., Elkord, Eyad, El-Rayes, Bassel, Feitelson, Mark A., Felsher, Dean W., Ferguson, Lynnette R., Fimognari, Carmela, Firestone, Gary L., Frezza, Christian, Fujii, Hiromasa, Fuster, Mark M., Generali, Daniele, Georgakilas, Alexandros G., Gieseler, Frank, Gilbertson, Michael, Green, Michelle F., Grue, Brendan, Guha, Gunjan, Halicka, Dorota, Helferich, William G., Heneberg, Petr, Hentosh, Patricia, Hirschey, Matthew D., Hofseth, Lorne J., Holcombe, Randall F., Honoki, Kanya, Hsu, Hsue-Yin, Huang, Gloria S., Jensen, Lasse D., Jiang, Wen G., Jones, Lee W., Karpowicz, Phillip A., Keith, W. Nicol, Kerkar, Sid P., Khan, Gazala N., Khatami, Mahin, Ko, Young H., Kucuk, Omer, Kulathinal, Rob J., Kumar, Nagi B., Kwon, Byoung S., Le, Anne, Lea, Michael A., Lee, Ho-Young, Lichtor, Terry, Lin, Liang-Tzung, Locasale, Jason W., Lokeshwar, Bal L., Longo, Valter D., Lyssiotis, Costas A., MacKenzie, Karen L., Malhotra, Meenakshi, Marino, Maria, Martinez-Chantar, Maria L., Matheu, Ander, Maxwell, Christopher, McDonnell, Eoin, Meeker, Alan K., Mehrmohamadi, Mahya, Mehta, Kapil, Michelotti, Gregory A., Mohammad, Ramzi M., Mohammed, Sulma I., Morre, D. James, Muralidhar, Vinayak, Muqbil, Irfana, Murphy, Michael P., Nagaraju, Ganji Purnachandra, Nahta, Rita, Niccolai, Elena, Nowsheen, Somaira, Panis, Carolina, Pantano, Francesco, Parslow, Virginia R., Pawelec, Graham, Pedersen, Peter L., Poore, Brad, Poudyal, Deepak, Prakash, Satya, Prince, Mark, Raffaghello, Lizzia, Rathmell, Jeffrey C., Rathmell, W. Kimryn, Ray, Swapan K., Reichrath, Jörg, Rezazadeh, Sarallah, Ribatti, Domenico, Ricciardiello, Luigi, Robey, R. Brooks, Rodier, Francis, Rupasinghe, H.P. Vasantha, Russo, Gian Luigi, Ryan, Elizabeth P., Samadi, Abbas K., Sanchez-Garcia, Isidro, Sanders, Andrew J., Santini, Daniele, Sarkar, Malancha, Sasada, Tetsuro, Saxena, Neeraj K., Shackelford, Rodney E., Shantha Kumara, H.M.C., Sharma, Dipali, Shin, Dong M., Sidransky, David, Siegelin, Markus David, Signori, Emanuela, Singh, Neetu, Sivanand, Sharanya, Sliva, Daniel, Smythe, Carl, Spagnuolo, Carmela, Stafforini, Diana M., Stagg, John, Subbarayan, Pochi R., Sundin, Tabetha, Talib, Wamidh H., Thompson, Sarah K., Tran, Phuoc T., Ungefroren, Hendrik, Vander Heiden, Matthew G., Venkateswaran, Vasundara, Vinay, Dass S., Vlachostergios, Panagiotis J., Wang, Zongwei, Wellen, Kathryn E., Whelan, Richard L., Yang, Eddy S., Yang, Huanjie, Yang, Xujuan, Yaswen, Paul, Yedjou, Clement, Yin, Xin, Zhu, Jiyue, and Zollo, Massimo

Published
2015
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50. Immune evasion in cancer: Mechanistic basis and therapeutic strategies

Author

Vinay, Dass S., Ryan, Elizabeth P., Pawelec, Graham, Talib, Wamidh H., Stagg, John, Elkord, Eyad, Lichtor, Terry, Decker, William K., Whelan, Richard L., Kumara, H.M.C. Shantha, Signori, Emanuela, Honoki, Kanya, Georgakilas, Alexandros G., Amin, Amr, Helferich, William G., Boosani, Chandra S., Guha, Gunjan, Ciriolo, Maria Rosa, Chen, Sophie, Mohammed, Sulma I., Azmi, Asfar S., Keith, W. Nicol, Bilsland, Alan, Bhakta, Dipita, Halicka, Dorota, Fujii, Hiromasa, Aquilano, Katia, Ashraf, S. Salman, Nowsheen, Somaira, Yang, Xujuan, Choi, Beom K., and Kwon, Byoung S.

Published
2015
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