In the right place at the right time: tissue-resident memory T cells in immunity to cancer

Abstract

Tissue-resident memory (Trm) cells have recently emerged as essential components of the immune response to cancer. Here, we highlight new studies that demonstrate how CD8⁺ Trm cells are ideally suited to accumulate in tumors and associated tissues, to recognize a wide range of tumor antigens (Ags), and to persist as durable memory. We discuss compelling evidence that Trm cells maintain potent recall function and serve as principal mediators of immune checkpoint blockade (ICB) therapeutic efficacy in patients. Finally, we propose that Trm and circulating memory T-cell compartments together form a formidable barrier against metastatic cancer. These studies affirm Trm cells as potent, durable, and necessary mediators of cancer immunity.

Figure 1.. Overview of Trm cell persistence and function in immunity to cancer.

(A) Tumor-Ag-specific Trm populations form across tissues where tumors grow and metastasize, with clonal counterparts in the blood; “?” denotes the unknown relationship between these compartments. (B) Multiple mechanisms enforce Trm cell persistence, retention, and fitness in the tumor microenvironment (TME). (C) Immune checkpoint blockade (ICB) therapy promotes clonal expansion and effector molecule production by Trm cells in tumors.