<p class="first" id="d399714e249">Carcinoma-associated fibroblasts (CAF) are key players
in the tumor microenvironment.
Here, we characterize four CAF subsets in breast cancer with distinct properties and
levels of activation. Two myofibroblastic subsets (CAF-S1, CAF-S4) accumulate differentially
in triple-negative breast cancers (TNBC). CAF-S1 fibroblasts promote an immunosuppressive
environment through a multi-step mechanism. By secreting CXCL12, CAF-S1 attracts CD4+CD25+
T lymphocytes and retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases
T lymphocyte survival and promotes their differentiation into CD25HighFOXP3High, through
B7H3, CD73, and DPP4. Finally, in contrast to CAF-S4, CAF-S1 enhances the regulatory
T cell capacity to inhibit T effector proliferation. These data are consistent with
FOXP3+ T lymphocyte accumulation in CAF-S1-enriched TNBC and show how a CAF subset
contributes to immunosuppression.
</p>