Syndecan‐2 peptide reduces the immunosuppressive properties of TASCs, reduces tumour growth and increases the percentage of activated T cells within the TME. A, TASCs were transfected with EV‐Fc control or S2‐Fc, 48 hours later protein extracts were prepared and PD‐L1 levels were determined by Western blot analysis. B, EV‐Fc or S2‐Fc expressing TASCs were cocultured with CD3/CD28‐activated peripheral blood mononuclear cells (PBMCs) at a ratio of 1:10. Flow cytometry of CFSE‐labelled CD4+ T cells was used to measure the level of proliferation. Data were compared by one‐way analysis of variance with Tukey's multiple comparison posttest. n = 3. C, EO771 tumours containing TASCs expressing S2‐Fc show a significant decrease in tumour growth compared EV‐Fc control tumours (n = 4 [EV‐Fc] n = 4 [F2‐Fc]). D, Tumours were excised and RT‐qPCR was performed to determine the levels of CXCR4 and PD‐L1. E, Flow cytometry analysis of tumours shows trends towards an increase in the number of CD8+, CD4−, CD62Llo, CD44hi and CD25+‐activated T cells. *P ≤ .05; **P ≤ .01; ***P ≤ .001 [Color figure can be viewed at wileyonlinelibrary.com]