Immunotherapy, represented by immune checkpoint inhibitors (ICIs), has significantly improved the clinical efficacy of treating malignant tumors. Antitumor responses mediated by immune checkpoint inhibitors depend on the infiltration of T cells capable of recognizing and killing tumor cells.
Recently, immune checkpoint inhibitors (ICIs), such as nivolumab and pembrolizumab, have been applied to an increasing number of cancer types, representing a standard treatment in clinical trials. 1, 2 Although immune checkpoint inhibitors have demonstrated clinical activity in a wide range of tumor types, a significant proportion of patients still do not respond to ICI therapy. 3
ICI-mediated antitumor responses depend on the expression of PD-L1 in tumors and the infiltration of T cells capable of recognizing and killing tumor cells. Immune cells such as CD8+ T cells are associated with longer survival in cancer patients and increased efficacy of immunotherapy. A lack of T cells in tumors can lead to resistance to immunotherapy.
The success of chimeric antigen receptor (CAR) T cell infusions for leukemia and lymphoma patients demonstrates the importance of T cells in antitumor immunity. Given the potential mechanisms of cancer immunotherapy, the infiltration of CD8+ T cells in tumors is important for the therapeutic response to ICIs. Based on the spatial distribution of cytotoxic immune cells in the tumor microenvironment (TME), tumors are classified into one of three basic immunophenotypes: immunoinflamed, immune-excluded, and immune-desert. Immune-inflamed tumors, also called "hot tumors," are characterized by high T-cell infiltration, increased interferon-γ (IFN-γ) signaling, PD-L1 expression, and a high tumor mutational burden (TMB). Tumors with an inflammatory phenotype tend to be more responsive to ACE inhibitors. Immune-excluded and immune-desert tumors can be described as "cold tumors." In immune-excluded tumors, CD8+ T lymphocytes are present only at the margins of invasion and do not infiltrate the tumor efficiently.
