American Association for Cancer Research
10780432ccr152657-sup-156931_2_supp_3326355_81kbtk.xlsx (41.2 kB)

Supplementary table 2 from Neoadjuvant Chemotherapy Modulates the Immune Microenvironment in Metastases of Tubo-Ovarian High-Grade Serous Carcinoma

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posted on 2023-03-31, 18:41 authored by Steffen Böhm, Anne Montfort, Oliver M.T. Pearce, Joanne Topping, Probir Chakravarty, Gemma L.A. Everitt, Andrew Clear, Jackie R. McDermott, Darren Ennis, Thomas Dowe, Amanda Fitzpatrick, Elly C. Brockbank, Alexandra C. Lawrence, Arjun Jeyarajah, Asma Z. Faruqi, Iain A. McNeish, Naveena Singh, Michelle Lockley, Frances R. Balkwill

PDS cohort


Swiss Cancer League

European Research Council

Cancer Research UK

Barts and The London Charity



Purpose: The purpose of this study was to assess the effect of neoadjuvant chemotherapy (NACT) on immune activation in stage IIIC/IV tubo-ovarian high-grade serous carcinoma (HGSC), and its relationship to treatment response.Experimental Design: We obtained pre- and posttreatment omental biopsies and blood samples from a total of 54 patients undergoing platinum-based NACT and 6 patients undergoing primary debulking surgery. We measured T-cell density and phenotype, immune activation, and markers of cancer-related inflammation using IHC, flow cytometry, electrochemiluminescence assays, and RNA sequencing and related our findings to the histopathologic treatment response.Results: There was evidence of T-cell activation in omental biopsies after NACT: CD4+ T cells showed enhanced IFNγ production and antitumor Th1 gene signatures were increased. T-cell activation was more pronounced with good response to NACT. The CD8+ T-cell and CD45RO+ memory cell density in the tumor microenvironment was unchanged after NACT but biopsies showing a good therapeutic response had significantly fewer FoxP3+ T regulatory (Treg) cells. This finding was supported by a reduction in a Treg cell gene signature in post- versus pre-NACT samples that was more pronounced in good responders. Plasma levels of proinflammatory cytokines decreased in all patients after NACT. However, a high proportion of T cells in biopsies expressed immune checkpoint molecules PD-1 and CTLA4, and PD-L1 levels were significantly increased after NACT.Conclusions: NACT may enhance host immune response but this effect is tempered by high/increased levels of PD-1, CTLA4, and PD-L1. Sequential chemoimmunotherapy may improve disease control in advanced HGSC. Clin Cancer Res; 22(12); 3025–36. ©2016 AACR.