Abstract 6109: Clonal relationship of B cells between tertiary lymphoid structures (TLSs) and tumor infiltrating lymphocytes (TILs) in advanced endometrial cancer

Abstract

Abstract Objective: Tertiary lymphoid structures (TLSs) are known to be a marker of peripheral inflammation. While high densities of TLSs were reported to be associated with longer patient survival in several cancer types, there is no direct evidence where B cells in TLSs(TLBs) are derived from and whether these clones are consistent with tumor infiltrating B cells (TIBs), in endometrial cancer. Methods: We analyzed the pathological distribution of TLSs and TIBs in human endometrial cancer samples using immunohistochemistry of a series of B cell markers and evaluated the relationship with patients’ clinical outcomes. Additionally, we micro-dissected six pairs of tumor nests and their neighbor TLSs and analyzed the clonal consistency between TLBs and TIBs using the sequencing of complementarity-determining region (CDR) of B cell receptor (BCR). Results: In 104 patients with endometrial cancer, TLSs were detected in 81 patients (78%), and the absence of TLS was related to worse progression-free survival (PFS) (HR, 0.15, P <0.01). Among TLS-detected cases, the high number of TIBs was significantly associated with better PFS (P<0.05). BCR analyses in the six patients found that three patients with advanced stage had a unique B cell clones in common between TLBs and TIBs, while the other three patients with early stage did not have any common B cell clones. The frequency of common B cell clones in the former three patients were 10.3% (5250/51146 reads), 9.7% (1873/19369 reads) and 3.0% (1034/34618 reads). Conclusion: TLSs and TIBs are associated with better prognosis in endometrial cancer. Common B cell clones were found in the advanced stage cases, suggesting that B cells may have gradually acquired immunospecificity in TLSs. Citation Format: Haruka Suzuki, Junzo Hamanishi, Meng Qin, Masayo Ukita, Akihiko Ueda, Shunsuke Kawahara, Koji Yamanoi, Taito Miyamoto, Shiro Takamatsu, Mana Taki, Yoko Hosoe, Takashi Kobayashi, Ken Yamaguchi, Masaki Mandai. Clonal relationship of B cells between tertiary lymphoid structures (TLSs) and tumor infiltrating lymphocytes (TILs) in advanced endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6109.