TIGIT and PD-1 mark intratumoral T cells with reduced effector function in B-cell non-Hodgkin lymphoma. Cancer immunology research Josefsson, S. E., Beiske, K., Blaker, Y. N., Forsund, M. S., Holte, H., Ostenstad, B., Kimby, E., Koksal, H., Walchli, S., Bai, B., Smeland, E. B., Levy, R., Kolstad, A., Huse, K., Myklebust, J. H. 2019


Checkpoint blockade can reverse T-cell exhaustion and promote antitumor responses. Although blocking the PD-1 pathway has been successful in Hodgkin lymphoma, response rates have been modest in B-cell non-Hodgkin lymphoma (NHL). Co-blockade of checkpoint receptors may therefore be necessary to optimize antitumor T-cell responses. Here, characterization of co-inhibitory receptor expression in intratumoral T cells from different NHL types identified TIGIT and PD-1 as frequently expressed co-inhibitory receptors. Tumors from NHL patients were enriched in CD8+ and CD4+ TEM cells that displayed high co-expression of TIGIT and PD-1, and co-expression of these checkpoint receptors identified T cells with reduced production of IFN-gamma, TNF-alpha and IL-2. The suppressed cytokine production could be improved upon in vitro culture in absence of ligands. Whereas PD-L1 was expressed by macrophages, the TIGIT ligands CD155 and CD112 were expressed by lymphoma cells in 39% and 50% of DLBCL cases and in some MCL cases, as well as by endothelium and FDCs in all NHLs investigated. Collectively, our results show that TIGIT and PD-1 mark dysfunctional T cells and suggest that TIGIT and PD-1 co-blockade should be further explored to elicit potent antitumor responses in patients with NHL.

View details for DOI 10.1158/2326-6066.CIR-18-0351

View details for PubMedID 30659053