AUTHOR=Cao Guangming , Hua Dingchao , Li Jinfeng , Zhang Xuefang , Zhang Zhiqiang , Zhang Bei , Bei Ting , Cui Lina , Chen Shiqing , Wang Shuzhen , Zhu Lei 

TITLE=Tumor immune microenvironment changes are associated with response to neoadjuvant chemotherapy and long-term survival benefits in advanced epithelial ovarian cancer: A pilot study

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1022942

DOI=10.3389/fimmu.2023.1022942

ISSN=1664-3224

ABSTRACT=<p>Little is known about the association between efficacy of neoadjuvant chemotherapy (NACT)/survival and the dynamic change of tumor immune environment (TIME) during treatment in epithelial ovarian cancer (EOC). This study investigated the TIME landscape of treatment-naive EOC tumors using multiplex immunofluorescence and associated the TIME before and after platinum-based NACT with treatment efficacy and prognosis in 33 patients with advanced EOC. NACT significantly increased the density of CD8<sup>+</sup> T cells (<italic>P</italic> = 0.033), CD20<sup>+</sup> B cells (<italic>P</italic> = 0.023), CD56 NK cells (<italic>P</italic> = 0.041), PD-1<sup>+</sup> cells (<italic>P</italic> = 0.042), and PD-L1<sup>+</sup>CD68<sup>+</sup> macrophages (<italic>P</italic> = 0.005) in the tissue specimens. Response to NACT was evaluated using CA125 response and chemotherapy response score (CRS). Compared with the non-responders, the responders displayed a larger proportion of tumors showing increase in the infiltration of CD20<sup>+</sup> cells (<italic>P</italic> = 0.046) and in the M1/M2 ratio (<italic>P</italic> = 0.038) as well as fewer tumors showing increase in the infiltration of CD56<sup>bright</sup> cells (<italic>P</italic> = 0.041). No association was found between pre-NACT TIME and response to NACT. Density of pre-NACT CD8<sup>+</sup> cells was positively associated with longer progression-free survival (PFS) (<italic>P</italic> = 0.011) and overall survival (OS) (<italic>P</italic> = 0.048). Post-NACT CD20<sup>+</sup> and CD163<sup>+</sup> macrophages (M2) infiltrates were associated with prolonged (<italic>P</italic> = 0.005) and shortened PFS (<italic>P</italic> = 0.021), respectively. Increase in the density of CD4<sup>+</sup> T cells was predictive for longer PFS (<italic>P</italic> = 0.022) and OS (<italic>P</italic> = 0.023). In the multivariate analysis, high density of CD8<sup>+</sup> cells pre-NACT (<italic>P</italic> = 0.042) were independently associated with improved OS.</p>