Technology meets TILs: Deciphering T cell function in the -omics era

Abstract

T cells are at the center of cancer immunology because of their ability to recognize mutations in tumor cells and directly mediate cancer cell killing. Immunotherapies to rejuvenate exhausted T cell responses have transformed the clinical management of several malignancies. In parallel, the development of novel multidimensional analysis platforms, such as single-cell RNA sequencing and high-dimensional flow cytometry, has yielded unprecedented insights into immune cell biology. This convergence has revealed substantial heterogeneity of tumor-infiltrating immune cells in single tumors, across tumor types, and among individuals with cancer. Here we discuss the opportunities and challenges of studying the complex tumor microenvironment with -omics technologies that generate vast amounts of data, highlighting the opportunities and limitations of these technologies with a particular focus on interpreting high-dimensional studies of CD8⁺ T cells in the tumor microenvironment.

Keywords: CD4; CD8; PD-1; T cell; bystander; cancer immunology; flow cytometry; immunotherapy; scRNA-seq; techniques; tumor-infiltrating lymphocytes.