Optimization of Immunotherapy Strategies Based on Spatiotemporal
Heterogeneity of Tumor-associated Tissue-resident Memory T Cells
Abstract
Tissue-resident memory T cells (TRMs) reside in peripheral tissues and
provide rapid immune defense against local infection and tumor.
Tumor-associated TRMs share common tissue-resident features and
formation mechanisms, representing some unique subsets of
tumor-infiltrating lymphocytes (TILs). However, differences in the tumor
microenvironment (TME) and tumor evolution stage result in TRMs
exhibiting temporal and spatial heterogeneity of phenotype and function
not only at different stages, before and after treatment, but also
between tumors origin from different tissue, primary and metastasis
cancer, and tumor and adjacent normal tissue. The infiltration of TRMs
is often associated with immunotherapy response and favorable prognosis,
however, due to different definition, it has been shown that some
subtypes of TRMs can also have a negative impact. Therefore, it is
crucial to precisely characterize the TRM subpopulations that can
influence the therapeutic efficacy and clinical prognosis of various
solid tumors. Here, we review the spatiotemporal heterogeneity of
tumor-associated TRMs, as well as the differences of their impact on the
clinical outcomes. We also explore the relationship between TRMs and
immune checkpoint blockade (ICB) and TIL therapy, providing insights
into potential new targets and strategies of immunotherapy.