TY - JOUR
T1 - Hallmarks of response, resistance, and toxicity to immune checkpoint blockade
AU - Morad, Golnaz
AU - Helmink, Beth A.
AU - Sharma, Padmanee
AU - Wargo, Jennifer A.
N1 - Funding Information:
We are grateful to Dr. Stephanie Watowich of MD Anderson Cancer Center for thoughtful comments and helpful suggestions. G.M. is supported by the National Institutes of Health ( 1F32CA260769-01 ). P.S. is a member of the Parker Institute for Cancer Immunotherapy. J.A.W. is supported by the National Institutes of Health ( 1R01CA219896-01A1 ), the Melanoma Research Alliance ( 4022024 ), American Association for Cancer Research Stand Up to Cancer ( SU2C-AACR-IRG-19-17 ), and the MD Anderson Cancer Center Melanoma Moonshot Program.
Funding Information:
We are grateful to Dr. Stephanie Watowich of MD Anderson Cancer Center for thoughtful comments and helpful suggestions. G.M. is supported by the National Institutes of Health (1F32CA260769-01). P.S. is a member of the Parker Institute for Cancer Immunotherapy. J.A.W. is supported by the National Institutes of Health (1R01CA219896-01A1), the Melanoma Research Alliance (4022024), American Association for Cancer Research Stand Up to Cancer (SU2C-AACR-IRG-19-17), and the MD Anderson Cancer Center Melanoma Moonshot Program. B.A.H. reports no conflicts of interest. G.M. is a co-inventor on US patents (PCT/US2019/022194, PCT/US2020/029556, PCT/US2020/046050) relating to extracellular vesicles. P.S. reports consulting, advisory roles, and/or stocks/ownership for Achelois, Adaptive Biotechnologies, Apricity Health, BioAlta, BioNTech, Codiak Biosciences, Constellation, Dragonfly Therapeutics, Forty-Seven Inc. Hummingbird, ImaginAb, Infinity Pharma, Jounce Therapeutics, Lave Therapeutics, Lytix Biopharma, Marker Therapeutics, Oncolytics, Phenomics, and Polaris Pharma and owns a patent licensed to Jounce Therapeutics. P.S. reports consulting, stock ownership, or advisory board membership for Achelois, Adaptive Biotechnologies, Apricity, BioAtla, BioNTech, Candel Therapeutics, Codiak, Dragonfly, Earli, Enable Medicine, Hummingbird, ImaginAb, Jounce, Lava Therapeutics, Lytix, Marker, PBM Capital, Phenomic AI, Polaris Pharma, Time Bioventures, and Trained Therapeutix and Venn Biosciences for an immediate family member. J.A.W. is a co-inventor on a US patent (PCT/US17/53,717) relating to the microbiome. J.A.W. reports speaker fees from Imedex, Dava Oncology, Omniprex, Illumina, Gilead, MedImmune, and BMS; consultant/advisor roles or advisory board membership for Roche-Genentech, Novartis, AstraZeneca, GSK, BMS, Merck/MSD, Biothera Pharma, and Microbiome DX; and receives clinical trial support from GSK, Roche-Genentech, BMS, and Novartis, all outside the current work.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/10/14
Y1 - 2021/10/14
N2 - Unprecedented advances have been made in cancer treatment with the use of immune checkpoint blockade (ICB). However, responses are limited to a subset of patients, and immune-related adverse events (irAEs) can be problematic, requiring treatment discontinuation. Iterative insights into factors intrinsic and extrinsic to the host that impact ICB response and toxicity are critically needed. Our understanding of the impact of host-intrinsic factors (such as the host genome, epigenome, and immunity) has evolved substantially over the past decade, with greater insights on these factors and on tumor and immune co-evolution. Additionally, we are beginning to understand the impact of acute and cumulative exposures—both internal and external to the host (i.e., the exposome)—on host physiology and response to treatment. Together these represent the current day hallmarks of response, resistance, and toxicity to ICB. Opportunities built on these hallmarks are duly warranted.
AB - Unprecedented advances have been made in cancer treatment with the use of immune checkpoint blockade (ICB). However, responses are limited to a subset of patients, and immune-related adverse events (irAEs) can be problematic, requiring treatment discontinuation. Iterative insights into factors intrinsic and extrinsic to the host that impact ICB response and toxicity are critically needed. Our understanding of the impact of host-intrinsic factors (such as the host genome, epigenome, and immunity) has evolved substantially over the past decade, with greater insights on these factors and on tumor and immune co-evolution. Additionally, we are beginning to understand the impact of acute and cumulative exposures—both internal and external to the host (i.e., the exposome)—on host physiology and response to treatment. Together these represent the current day hallmarks of response, resistance, and toxicity to ICB. Opportunities built on these hallmarks are duly warranted.
UR - http://www.scopus.com/inward/record.url?scp=85117138808&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2021.09.020
DO - 10.1016/j.cell.2021.09.020
M3 - Review article
C2 - 34624224
AN - SCOPUS:85117138808
VL - 184
SP - 5309
EP - 5337
JO - Cell
JF - Cell
SN - 0092-8674
IS - 21
ER -