Platelets are major suppressors of T cell function

Using T cells directly or indirectly as therapeutic targets for cancer has revolutionized cancer immunotherapy. Removal of immunosuppressive factors by the use of checkpoint inhibitors such as PD-1, PD-L1 and CTLA-4, as well as adoptive transfer of engineered T cells, highlight therapeutic approaches that are showing great promise in the clinic.

Multiple suppressive mechanisms in the tumour micro-environment have been implicated in the resistance to checkpoint blockade or the lack of response to adoptive T cell transfer.

In this article, the authors have initially shown that genetic inhibition of platelets enhances adoptive T cell therapy of the B16 melanoma model. Due to the lack of platelets in the T cell zones of lymphoid organs, the authors hypothesised that a soluble factor was responsible for the immunosuppressive properties of platelets. Using flow cytometry after size exclusion chromatography of platelet releasate, the authors have identified that TGFβ significantly inhibits intracellular IFNγ and TNFα in both human and mouse CD8+ T cells.

Blockade of TGFβ had partial effect in vivo. However, platelet-specific genetic deletion of GARP, a surface docking receptor that is important for tethering TGFβ to the cell surface, significantly improved adoptive T cell transfer in the B16 melanoma and MC38 colon cancer models.

The prevalence of TGFβ in the tumour microenvironment has historically been attributed to cancer and stromal cells. However, this study highlights the contribution of platelets to the immunosuppressive tumour microenvironment via cell surface TGFβ‑docking receptor GARP.

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Epistem's Validated Models and Cytometric Expertise

At Epistem, we currently offer validated models to address immune function in tumour bearing mice.

Our detailed flow cytometric expertise can further assess the identity of tumour infiltrating and peripheral cell populations such as CD8+ T cells, MDCSs and regulatory T cells, by surface identification of key molecules, or the intracellular mediators they express (cytokines, transcription factors).

Rachidi et al. Sci immunol. 2, eaai7911 (2017).

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