Towards T Cell Immunotherapies Targeting Senescent Cancer Cells

A robust discussion is underway in the cancer research community regarding the merits of targeting senescent cells for destruction as a part of cancer therapy. While it is generally agreed that clearing lingering senescent cells following successful treatment with present cancer therapies is a good idea, as those senescent cells contribute to the greater burden of age-related disease and mortality observed in cancer survivors, it is less clear that destroying senescent cancer cells during treatment of the cancer will always provide a net benefit. Those senescent cells can in some cases contribute to the destruction of the cancer rather than enable its growth. Nonetheless, researchers here argue that adapting T cell immunotherapies to target senescent tumor cells is a promising avenue of investigation.

The exploitation of the patient's immune system to eliminate cancer cells has long been tested through the development of innovative strategies with remarkable success and high expectations. Our growing understanding of the immune system has allowed the design of novel anticancer therapies. However, tumor cells are generally poor antigen-presenting cells, evading the immune response in early stages of the pathophysiology and restricting immunotherapeutic efficacy to only a minor group of cancers. Nevertheless, targeting of senescent cells in the context of cancer and aging may upsurge as an alternative to this critical limitation, through the selective activation of a T cell-specific response against senescent cells within the tumor or its vicinity.

Recent evidence supports the use of tumor-associated senescent cells (TASCs) as sources of peptide antigens and adjuvants for anticancer vaccine development. Their senescence-associated secretory phenotype (SASP) provides abundant release of stimulatory cytokines, which, in conjunction with high levels of antigen presentation, generates a robust tumor specific T cell response. As discussed here, this approach will potentiate their adjuvanticity in cancer targeting, allowing the design of stronger and directed immunotherapeutic strategies. Moreover, since cancer and senescent cells share common antigens, this immunotherapeutic approach could also be effective against aging and age-related diseases. Therefore, cancer immunotherapy based on TASCs and other types of senescent cells may achieve exciting outcomes beyond cancer therapy.


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