Immunological correlatives of durable responses and survival benefit for patients with cervical cancer in a trial of combined chemotherapy and immune therapy.

Abstract

5537 Background: Recurrent, metastatic, or persistent cervical cancer is largely an incurable disease due to lack of effective therapies. New treatment strategies are needed to provide long-term anti-tumor responses. We sought to gain insight into the immune pathways contributing to treatment response to immunotherapy. Methods: Fourteen patients with recurrent, persistent, or metastatic cervical cancer were enrolled in a single-arm phase II clinical trial (NCT03367871) with the combination of chemotherapy, bevacizumab and pembrolizumab regardless of tumor PD-L1 status. We designed a 40-color full spectrum flow cytometry panel to profile the protein markers of immune cells in peripheral blood mononuclear cells (PBMCs) at the single cell level to assess immunological correlates in blood with patients' anti-tumor responses. Results: In this trial with a cohort of predominantly Black and Hispanic patients (93%), 50% had durable responses to a combination therapy, and no difference was observed in the combined PD-L1 score (CPS) between responders and non-responders. With 40-color flow cytometry multiplex assays, we detected several differences between the non-responders and responders within the B and T cell populations. Within the B cell population, we observed a significant increase in the HLA+CD200hi B cells, a potentially suppressive cell subset, within the non-responders while among the responders we observed an increase in the number of HLA+CD200lo B cells. This HLA+CD200lo subset was mainly composed of IgD-CD27- memory B cells, a population suggested to have effector function. Moreover, the HLA+CD200hi B cell population contained a higher percentage of PD-L1 expressing cells than the HLA+CD200lo population, further supporting the suggestion that the HLA+CD200hi population may be an immunosuppressive subset. Within the T cell compartment, we observed an increase in the number of CD4+CD69+ T cells, which represent an activated CD4 T cell population, in the responder group compared to the non-responder group. The number of activated CD4+ T cells was observed to correlate (r = 0.5) with the HLA+CD200hi B cell subset. Conclusions: This study identified novel immunological correlates in peripheral blood that were associated with durable antitumor responses and survival benefit for cervical cancer patients. These results suggest a role for T-B collaboration in effective antitumor immunity induced by combination of chemotherapy and immune therapy against cervical cancer. Clinical trial information: NCT03367871.