Impact of chemotherapy alone or in combination with an anti-angiogenic on the immune tumor microenvironment (TME) of ovarian cancer: Data from the randomized CHIVA trial (a GINECO –GINEGEPS study).

Abstract

6011 Background: The neoadjuvant setting is an excellent opportunity to study ‘ in vivo’ the biological impact of treatment on tumor cells and the immune TME. Both chemotherapy and anti-angiogenics may have immunomodulatory properties which could prime the TME and increase effectiveness of immunotherapeutic agents. We performed comprehensive multiplexed immune biomarker analyses on paired tumor samples at diagnosis and after 3 cycles of neoadjuvant carboplatin+paclitaxel (CP) +/- the anti-angiogenic tyrosine kinase inhibitor nintedanib (N) in the randomized CHIVA trial. Methods: Patients were randomized 2:1 to CP + N or placebo for 3 cycles prior to interval debulking, samples were evaluable for immune profiling for 124 pts at diagnosis and 107 at surgery from the CHIVA trial. For 86 patients matched paired samples were available. Multiplexed IF or IHC panels were performed for CD4, CD3, CD8, CK, Granzyme B, FOXP3, CD68, CD163 and DC-Lamp. Wilcoxon tests were used to compare measurements. Results: At diagnosis the most abundant cells were CD8+ and CD4+ cells (median=118 and 119cells/mm2, respectively) compared to Foxp3+ TRegs (median=30/mm2). Among the myeloid lineage, the proportion of CD68+ (M1) and CD163+ (M2) macrophages was balanced, while mature dentritic cells (DC) represented <5% of myeloid cells. In the whole population, regardless of arm, neoadjuvant platinum-based treatment significantly increased CD4+ (p=0.03) and CD8+ infiltration (p=0.009), decreased FOXP3+ cells (p=0.01), and these differences pre- and post-treatment remained significant when analysis was restricted to pts with paired samples. Mature DC also increased significantly with neoadjuvant treatment (p=0.0003), there was no significant modification in CD68+ or CD163+ macrophages. Changes in immune parameters did not differ significantly between the CP+B vs CP+placebo arms. Conclusions: Neoadjuvant treatment has a profound impact on the immune cell composition of the TME in advanced OC. However this change seems to be mainly mediated by platinum+paclitaxel chemotherapy rather than the anti-angiogenic tyrosine kinase inhibitor nintedanib.