Myeloid cells meet CD8+ T cell exhaustion in cancer: What, why and how

Exhausted T cell (Tex) is a specific state of T cell dysfunction, in which these T cells gradually lose their effector function and change their phenotype during chronic antigen stimulation. The enrichment of exhausted CD8⁺ T cell (CD8⁺ Tex) in the tumor microenvironment is one of the important reasons leading to the poor efficacy of immunotherapy. Recent studies have reported many reasons leading to the CD8⁺ T cell exhaustion. In addition to cancer cells, myeloid cells can also contribute to T cell exhaustion via many ways. In this review, we discuss the history of the concept of exhaustion, CD8⁺ T cell dysfunction states, the heterogeneity, origin, and characteristics of CD8⁺ Tex. We then focus on the effects of myeloid cells on CD8⁺ Tex, including tumor-associated macrophages (TAMs), dendritic cells (DCs) and neutrophils. Finally, we systematically summarize current strategies and recent advancements in therapies reversing and CD8⁺ T cell exhaustion.