Abstract
Immune checkpoint inhibitors (ICI) such as PD-1/PD-L1 antibodies (Abs) and CTLA4 Abs and T cell-based adoptive cell therapies are effective for patients with various cancers. However, response rates of ICI monotherapies are still limited due to lack of immunogenic antigens and various immune-resistant mechanisms. The latter includes adaptive immune resistance that is caused by anti-tumor T cells (e.g. PD-L1 induced by IFN-γ from T cells) and primary immune resistance that is caused by cancer cells (e.g. immunosuppressive cytokines produced by cancer cells). Further understanding of the immune-resistant mechanisms, which may be possible through comparative analyses of responders and non-responders to the immunotherapies, will lead to the identification of new diagnostic biomarkers and therapeutic targets for development of effective cancer immuno therapies.
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Acknowledgements
This work was supported by Grants-in-aid for Scientific Research (26221005) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and the Project for Cancer Research And Therapeutic Evolution (P-CREATE) (16cm0106305h0001) from Japan Agency for Medical Research and Development (AMED).
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Y. Kawakami is an advisor for Taiho Pharma Co. Ltd., has received honoraria from Ono Pharmaceutical Co. Ltd., Bristol-Myers Squibb, MSD, Chugai, AstraZeneca, and has received research funding from Ono Pharmaceutical Co. Ltd., Bristol-Myers Squibb, Kowa, JSR, Dainippon Sumitomo Pharma Co. Ltd., and Carna BioSciences, Inc. Other co-authors have no conflict of interest.
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Kawakami, Y., Ohta, S., Sayem, M.A. et al. Immune-resistant mechanisms in cancer immunotherapy. Int J Clin Oncol 25, 810–817 (2020). https://doi.org/10.1007/s10147-019-01611-x
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DOI: https://doi.org/10.1007/s10147-019-01611-x