Regulation of myeloid cells by activated T cells determines the efficacy of PD-1 blockade.

Eissler N, Mao Y, Brodin D, Reuterswärd P, Andersson Svahn H, Johnsen JI, Kiessling R, Kogner P

Oncoimmunology 5 (12) e1232222 [2016-09-09; online 2016-09-09]

Removal of immuno-suppression has been reported to enhance antitumor immunity primed by checkpoint inhibitors. Although PD-1 blockade failed to control tumor growth in a transgenic murine neuroblastoma model, concurrent inhibition of colony stimulating factor 1 receptor (CSF-1R) by BLZ945 reprogrammed suppressive myeloid cells and significantly enhanced therapeutic effects. Microarray analysis of tumor tissues identified a significant increase of T-cell infiltration guided by myeloid cell-derived chemokines CXCL9, 10, and 11. Blocking the responsible chemokine receptor CXCR3 hampered T-cell infiltration and reduced antitumor efficacy of the combination therapy. Multivariate analysis of 59 immune-cell parameters in tumors and spleens detected the correlation between PD-L1-expressing myeloid cells and tumor burden.

Affiliated researcher

PubMed 28123870

DOI 10.1080/2162402X.2016.1232222

Crossref 10.1080/2162402X.2016.1232222

pii: 1232222
pmc: PMC5214950