Tissue-resident memory T cells in gastrointestinal cancer immunology and immunotherapy: ready for prime time?

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.

Harnessing Antitumor CD4+ T Cells for Cancer Immunotherapy.

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.

A new workflow combining magnetic cell separation and impedance-based cell dispensing for gentle, simple and reliable cloning of specific CD8+ T cells.

Reverse immunology has open the door to innovative cancer immunotherapy strategies such as immunogenic antigen-based vaccination and transgenic T cell receptor (TCR)-based adoptive cell transfer. This approach enables the identification of immunogenic tumor specific antigen derived peptides. One of the major challenges is the rapid selection of antigen-specific CD8+ T cell clones. Thus, IFNγ-producing CD8+ T cells magnetic sorting combined with limiting dilution cloning approach represents the most common method of specific T cell cloning. However, during plate setup several wells will not contain T cells whereas others will contain mixed population of T cells. In this case, a re-cloning step is required which make limiting dilution based cloning a laborious, inefficient, expensive and a time-consuming method. To address these obstacles, here we present a novel 2-step workflow combining simple, affordable and gentle magnetic cell separation followed by single cell isolation using a device called DispenCell-S1. We aimed to compare this new workflow with the traditional limiting dilution method using in vitro generated antigen-specific CD8+ T cells. Herein, we reported the reliability of DispenCell-S1 method and its efficiency in T cell clones isolation.