TY - JOUR
T1 - Hematopoietic versus solid cancers and T cell dysfunction: Looking for similarities and distinctions
AU - Montironi, Chiara
AU - Muñoz-Pinedo, Cristina
AU - Eldering, Eric
N1 - Funding Information: Funding: This work was supported by the EU’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement 766214 (META-CAN). CMP’s lab is funded by the CERCA Program/Generalitat de Catalunya and by Ministerio de Ciencia, Innovación y Ministerio de Ciencia e Innovación, part of Agencia Estatal de Investigación (AEI), through the Generación de Conocimiento grant, number PID2019-107213GB-I00/DOI: 10.13039/501100011033. Funding Information: This work was supported by the EU?s Horizon 2020 Research and Innovation Programme under the Marie Sk?odowska-Curie Grant Agreement 766214 (META-CAN). CMP?s lab is funded by the CERCA Program/Generalitat de Catalunya and by Ministerio de Ciencia, Innovaci?n y Ministerio de Ciencia e Innovaci?n, part of Agencia Estatal de Investigaci?n (AEI), through the Generaci?n de Conocimiento grant, number PID2019-107213GB-I00/DOI: 10.13039/501100011033. We thank our colleagues Anne W.J. Martens, Department of Experimental Immunology, Cancer Center Amsterdam, Amsterdam Infection & Immunity Institute, and Lymphoma and Myeloma Center Amsterdam, Amsterdam UMC, University of Amsterdam, The Netherlands, Ann Zeuner, Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanit?, Rome, Italy, Joris D. Veltman, Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands and Rosalie M. Luiten, Netherlands Institute for Pigment Disorders, Department of Dermatology, Amsterdam Infection and Immunity Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands, for reading the manuscript, comments and criticisms. Publisher Copyright: © 2021 by the authors. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/2
Y1 - 2021/1/2
N2 - Cancer cells escape, suppress and exploit the host immune system to sustain themselves, and the tumor microenvironment (TME) actively dampens T cell function by various mechanisms. Over the last years, new immunotherapeutic approaches, such as adoptive chimeric antigen receptor (CAR) T cell therapy and immune checkpoint inhibitors, have been successfully applied for refractory malignancies that could only be treated in a palliative manner previously. Engaging the anti-tumor activity of the immune system, including CAR T cell therapy to target the CD19 B cell antigen, proved to be effective in acute lymphocytic leukemia. In low-grade hematopoietic B cell malignancies, such as chronic lymphocytic leukemia, clinical outcomes have been tempered by cancer-induced T cell dysfunction characterized in part by a state of metabolic lethargy. In multiple myeloma, novel antigens such as BCMA and CD38 are being explored for CAR T cells. In solid cancers, T cell-based immunotherapies have been applied successfully to melanoma and lung cancers, whereas application in e.g., breast cancer lags behind and is modestly effective as yet. The main hurdles for CAR T cell immunotherapy in solid tumors are the lack of suitable antigens, anatomical inaccessibility, and T cell anergy due to immunosuppressive TME. Given the wide range of success and failure of immunotherapies in various cancer types, it is crucial to comprehend the underlying similarities and distinctions in T cell dysfunction. Hence, this review aims at comparing selected, distinct B cell-derived versus solid cancer types and at describing means by which malignant cells and TME might dampen T cell anti-tumor activity, with special focus on immunometabolism. Drawing a meaningful parallel between the efficacy of immunotherapy and the extent of T cell dysfunction will shed light on areas where we can improve immune function to battle cancer.
AB - Cancer cells escape, suppress and exploit the host immune system to sustain themselves, and the tumor microenvironment (TME) actively dampens T cell function by various mechanisms. Over the last years, new immunotherapeutic approaches, such as adoptive chimeric antigen receptor (CAR) T cell therapy and immune checkpoint inhibitors, have been successfully applied for refractory malignancies that could only be treated in a palliative manner previously. Engaging the anti-tumor activity of the immune system, including CAR T cell therapy to target the CD19 B cell antigen, proved to be effective in acute lymphocytic leukemia. In low-grade hematopoietic B cell malignancies, such as chronic lymphocytic leukemia, clinical outcomes have been tempered by cancer-induced T cell dysfunction characterized in part by a state of metabolic lethargy. In multiple myeloma, novel antigens such as BCMA and CD38 are being explored for CAR T cells. In solid cancers, T cell-based immunotherapies have been applied successfully to melanoma and lung cancers, whereas application in e.g., breast cancer lags behind and is modestly effective as yet. The main hurdles for CAR T cell immunotherapy in solid tumors are the lack of suitable antigens, anatomical inaccessibility, and T cell anergy due to immunosuppressive TME. Given the wide range of success and failure of immunotherapies in various cancer types, it is crucial to comprehend the underlying similarities and distinctions in T cell dysfunction. Hence, this review aims at comparing selected, distinct B cell-derived versus solid cancer types and at describing means by which malignant cells and TME might dampen T cell anti-tumor activity, with special focus on immunometabolism. Drawing a meaningful parallel between the efficacy of immunotherapy and the extent of T cell dysfunction will shed light on areas where we can improve immune function to battle cancer.
KW - Immunotherapy
KW - Metabolism
KW - Microenvironment
KW - T cell dysfunction
KW - TME
UR - http://www.scopus.com/inward/record.url?scp=85099546414&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers13020284
DO - https://doi.org/10.3390/cancers13020284
M3 - Article
C2 - 33466674
SN - 2072-6694
VL - 13
SP - 1
EP - 20
JO - Cancers
JF - Cancers
IS - 2
M1 - 284
ER -