T ‐cell cross‐reactivity may explain the large variation in how cancer patients respond to checkpoint inhibitors

Abstract The therapeutic use of the immune system to specifically attack tumours has been a long‐standing vision among tumour immunologists. Recently, the use of checkpoint inhibitors to turn‐off immunosuppressive signals has proven to be effective in enhancing T‐cell reactivity against patient‐specific neoantigens, resulting from somatic mutations. Several of the identified T‐cell epitopes share similarity with common bacterial and viral antigens, suggesting the involvement of pre‐existing microbial cross‐reactive T cells in rapid and durable tumour regression seen in some patients. This notion of T‐cell cross‐reactivity is further supported by the findings that intestinal bacteria can influence checkpoint‐blockade therapy. Moreover, early data indicate the presence of such T cells in long‐term survival breast cancer patients. This review highlights the main challenges for cancer immunotherapy and discusses the potential contribution of T‐cell cross‐reactivity in cancer immunotherapy and whether it can be used as a biomarker to predict the responsiveness to checkpoint inhibitors.
Source: Scandinavian Journal of Immunology - Category: Allergy & Immunology Authors: Tags: REVIEW ARTICLE Source Type: research