CD47 is a potent ‘don’t eat me’ signal that promotes tumor immune evasion by inhibiting phagocytosis by macrophages. In OC, CD47 is reported to be overexpressed and its expression correlates with poor prognosis and shorter survival. However, how CD47 expression relates to other key features in the immune tumor microenvironment (iTME) or changes under treatment remains unknown. Here, we evaluated CD47 expression on a cohort of OC tumors from 188 patients at diagnosis and after NACT in a clinical trial, CHIVA, and its correlation with other iTME features.
105 patients in CHIVA were evaluable for CD47 expression by IHC in paired samples pre- and post-NACT. CD47 expression was scored by H-score: staining intensity (0, +1, +2, +3) x % cells positive (0-300). CD8+ T cells scored as number of positive cells, T cell co-regulators (PDL1, TIM3, LAG3) scored as % positive cells. The association of CD47 H‐score with other immune features was evaluated (Pearson test).
Among 105 patients, 75% had serous OC (HGOC). CD47 median expression at baseline was high at 200 (SD=56) with 0% completely negative. CD47 expression at baseline was positively correlated with other immune tolerance mediators such as the M2 marker CD163 (p=0.003) or T cell exhaustion markers such as PD-L1 (p=0.005) and TIM-3 (p=0.006). However, correlation between CD47 and CD163 was lost after NACT (p=0.6). Interestingly, the expression of CD47 appears to be positively correlated with the presence of CD8+ T cells, but only after NACT (p=0.04). Evaluation of CD47 expression in paired samples before and after chemotherapy demonstrated a significant decrease (paired Wilcoxon ranked test, p<0.001) suggesting immunomodulatory effects of chemotherapy on the iTME of OC.
We show that NACT increases CD8+ T cell infiltration and decreased CD47 expression in support of favorable immunomodulatory effects on the iTME in HGOC. In addition, our data suggest that immune escape in HGOC could be the result of concerted overexpression of multiple immune suppressor molecules. Inhibiting both CD47 and other features from the iTME could represent an attractive strategy to enhance anti-tumor immunity in HGOC.
NCT01583322