Over the past decades, CD4+ T cells have been considered as a supporting actor in the fields of cancer immunotherapy. Until recently, accumulating evidence has demonstrated the critical role of CD4+ T cells during antitumor immunity. CD4+ T cells can either suppress or promote the antitumor cytotoxic CD8+ T cell responses, either in secondary lymphoid organs or in the tumor. In this review, we provide an overview of the multifaceted role of different CD4+ T cell subsets in cancer immune response and their contribution during cancer therapies. Specifically, we focus on the latest progress regarding the impact of CD4+ T cell modulation on immunotherapies and other cancer therapies and discuss the prospect for harnessing CD4+ T cells to control tumor progression and prevent recurrence in patients.
Tissue-resident memory T (TRM) cells have emerged as immune sentinels that patrol the tissue microenvironment and orchestrate localized antitumor immunity in various solid cancers. Recent studies have revealed that TRM cells are key players in cancer immunosurveillance, and their involvement has been linked to favorable responses to immunotherapy as well as general better clinical outcome in cancer patients. In this review, we provide an overview of the major advances and recent findings regarding TRM cells phenotype, transcriptional and epigenetic regulation in cancer with a special focus on gastrointestinal tumors. Finally, we highlight the exciting clinical implication of TRM cells in these types of tumors.
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