Dynamic CD8+ T Cell Cooperation with Macrophages and Monocytes for Successful Cancer Immunotherapy

Simple Summary Innate and adaptive immunity mutually regulate one another in a dynamic fashion during immune responses. In infectious contexts, positive interactions between macrophages, monocytes and T cells are well recognized, but this is not the case in the field of cancer, where the growth of tumors disturbs the immune response. However, recent advances revealed that successful immunotherapy profoundly remodels the tumor microenvironment, promoting the activation of both T cells and myeloid cells. This review highlights the studies that hint at positive CD8(+) T cell cooperation with monocytes and macrophages in this context, and discusses the potential mechanisms behind this. The essential roles endorsed by macrophages and monocytes are well established in response to infections, where they contribute to launching the differentiation of specific T-lymphocytes for long-term protection. This knowledge is the result of dynamic studies that can inspire the cancer field, particularly now that cancer immunotherapies elicit some tumor regression. Indeed, immune responses to cancer have mainly been studied after tumors have escaped immune attacks. In particular, the suppressive functions of macrophages were revealed in this context, introducing an obvious bias across the literature. In this review, we will focus on the ways inwhich monocytes and macrophages cooperate with T-lymphocytes, leading to successful immune responses. We will bring together the preclinical studies that have revealed the existence of such positive cooperation in the cancer field, and we will place particular emphasis on proposing the underlying mechanisms. Finally, we will give some perspectives to decipher the functional roles of such T-cell and myeloid cell interactions in the frame of human cancer immunotherapy.

Automated summary

In the field of cancer, the growth of tumors disturbs the immune response, but recent advances in immunotherapy have shown that successful treatment can remodel the tumor microenvironment and activate T cells and myeloid cells. This review focuses on the positive cooperation between CD8(+) T cells, monocytes, and macrophages in cancer immunotherapy, and discusses the underlying mechanisms.