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).

person Alexandra Leary Gustave-Roussy Cancer Campus, Villejuif, and GINECO, Paris, France info_outline Alexandra Leary, Laure Chardin, Catherine Genestie, Alain Lortholary, Jerome Alexandre, Thibault De La Motte Rouge, Veronique D'hondt, Anne Floquet, Aude-Marie Savoye, Nicolas Delanoy, Céline Gavoille, Benoit You, Julien Grenier, Elisa Yaniz-Galende

Authors person Alexandra Leary Gustave-Roussy Cancer Campus, Villejuif, and GINECO, Paris, France info_outline Alexandra Leary, Laure Chardin, Catherine Genestie, Alain Lortholary, Jerome Alexandre, Thibault De La Motte Rouge, Veronique D'hondt, Anne Floquet, Aude-Marie Savoye, Nicolas Delanoy, Céline Gavoille, Benoit You, Julien Grenier, Elisa Yaniz-Galende Organizations Gustave-Roussy Cancer Campus, Villejuif, and GINECO, Paris, France, Gustave Roussy Cancer Center, INSERM U981, Villejuif, France, Centre Catherine de Sienne, Hôpital Privé du Confluent, Nantes, France, Université de Paris Cité, AP-HP, Hôpital Cochin, Paris, and GINECO, Paris, France, Centre Eugène Marquis, Rennes, and GINECO, Paris, France, Institut du Cancer de Montpellier (ICM), Montpellier, France, Institut Bergonié, Bordeaux, France, Medical Oncology Department, Institut Jean Godinot, Reims, France, Institut du Cancer Paris CARPEM, Assistance Publique Hôpitaux de Paris (AP-HP), APHP. Centre service d'oncologie médicale, Hôpital Européen Georges Pompidou, Paris, Paris, France, ICL- Alexis Vautrin Center, Vandoeuvre Les Nancy, France, Centre Hospitalier Lyon Sud, Pierre-Benite and GINECO, Paris, France, Institut du Cancer Avignon-Provence, Avignon, and GINECO, Paris, France Abstract Disclosures Research Funding Pharmaceutical/Biotech Company AstraZeneca 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.

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