Immune features of ovarian tumors with a good response to neo-adjuvant chemotherapy in combination with an anti-PD-L1 alone or with an anti-CTLA4: Data from the randomized IneOV trial (a GINECO study).

Abstract

5586 Background: We have shown that chemotherapy may have immunomodulatory properties and prime the tumor microenvironment (TME) by recruiting cytotoxic immune cells. We previously reported that neoadjuvant chemotherapy (NACT) associated with Durvalumab (D) +/- Tremelimumab (T) resulted in encouraging complete resection (70%) and complete pathological response (18%) rates in patients with unresectable ovarian cancer. Here, we aimed to 1) characterize the immune TME at baseline of responders compared to non-responders and 2) describe changes in immune TME in paired tumor samples at diagnosis and after 3 cycles of NACT with D +/- T in the randomized IneOV trial. Methods: Tumor samples from IneOV trial (55 at diagnosis, 40 after treatment) were analyzed for CD3+, CD68+ and CD20+ by multiplexed immunohistochemistry. Stromal and intra-epithelial TILs were scored as percentage of positive surface. Patients were classified as good pathological responders (pR) (CRS3) or pathological non-responders (pNR) (CRS1 or 2). Intra-tumoral T cell infiltration was described as High or Low (intraepithelial (ie)CD3+ > median vs < , respectively). Non parametric statistical tests were used. We evaluated the correlation of the markers with each others (Spearman test) and with pathological response rate (Mann-Withney test). Results: At diagnosis, in the intra-epithelial compartment of the TME, the most abundant cells were macrophages (median ieCD68+ = 3,4) compared to T (ieCD3+ = 1.1), B (ieCD20+ ND) ANOVA p-value = 0.002 and < 0.0001 respectively . In individual tumors, infiltration by the 3 different immune subsets was poorly correlated suggesting immune TME heterogeneity in OC. Pathological response was evaluable in 64 patients: 19 pR and 45 pNR. At diagnosis, CD3+ (p = 0.02) and CD68+ (p = 0.006) infiltration was significantly higher in pR tumors compared to pNR. Most of pR (76%) had high intra-tumoral CD3+ infiltration versus 39% in pNR (p = 0.011). After treatment, tumors with pR showed significantly greater CD3+ intra-epithelial infiltration compared to pNR (p = 0.047). Conclusions: Our results suggest that good pathological response to NACT +D+/-T is associated with high levels of both T cells and macrophages in iTME at baseline, and increased intratumoral T cell infiltration post-treatment. Work is ongoing to further characterize the iTME, especially in pNR to identify other strategies to enhance the anti-tumor immune response. Clinical trial information: NCT03249142 .