The Potential of Tissue-Resident Memory T Cells for Adoptive Immunotherapy against Cancer

Tissue-resident memory T cells (T_RM) comprise an important memory T cell subset that mediates local protection upon pathogen re-encounter. T_RM populations preferentially localize at entry sites of pathogens, including epithelia of the skin, lungs and intestine, but have also been observed in secondary lymphoid tissue, brain, liver and kidney. More recently, memory T cells characterized as T_RM have also been identified in tumors, including but not limited to melanoma, lung carcinoma, cervical carcinoma, gastric carcinoma and ovarian carcinoma. The presence of these memory T cells has been strongly associated with favorable clinical outcomes, which has generated an interest in targeting T_RM cells to improve immunotherapy of cancer patients. Nevertheless, intratumoral T_RM have also been found to express checkpoint inhibitory receptors, such as PD-1 and LAG-3. Triggering of such inhibitory receptors could induce dysfunction, often referred to as exhaustion, which may limit the effectiveness of T_RM in countering tumor growth. A better understanding of the differentiation and function of T_RM in tumor settings is crucial to deploy these memory T cells in future treatment options of cancer patients. The purpose of this review is to provide the current status of an important cancer immunotherapy known as TIL therapy, insight into the role of T_RM in the context of antitumor immunity, and the challenges and opportunities to exploit these cells for TIL therapy to ultimately improve cancer treatment.