Density and maturity of peritumoral tertiary lymphoid structures in oesophageal squamous cell carcinoma predicts patient survival and response to immune checkpoint inhibitors

食管鳞状细胞癌肿瘤周围三级淋巴结构的密度和成熟度可预测患者的生存率和对免疫检查点抑制剂的反应

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作者:Yoshinori Hayashi, Tomoki Makino, Eiichi Sato, Kenji Ohshima, Yuya Nogi, Takashi Kanemura, Keiichiro Honma, Kotaro Yamashita, Takuro Saito, Koji Tanaka, Kazuyoshi Yamamoto, Tsuyoshi Takahashi, Yukinori Kurokawa, Hiroshi Miyata, Kiyokazu Nakajima, Hisashi Wada, Eiichi Morii, Hidetoshi Eguchi, Yuichir

Background

Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates in non-lymphoid tissues, which are associated with improved prognosis in some cancer types. This study aimed to investigate the clinical significance of TLSs in oesophageal cancer (EC).

Conclusion

The density and maturity of peritumoral TLSs are useful parameters for predicting long-term survival and response to anti-PD-1 antibody treatment in EC patients.

Methods

In a series of 316 EC surgical specimens from two different institutes, we evaluated the density and maturity of peritumoral TLSs using haematoxylin/eosin, immunohistochemistry, and multiplex immunofluorescence staining. We analysed the association between TLSs and clinicopathological parameters. The clinical significance of TLSs was further evaluated in a different cohort of 34 patients with recurrent EC treated with anti-PD-1 antibody.

Results

Tumours with high TLS density predominantly consisted of matured TLSs. High TLS density was significantly associated with less advanced tumour stage, absence of lymphatic/vascular invasion, better serum nutrition parameters (neutrophils count, albumin, neutrophil-to-lymphocyte ratio, and prognostic nutritional index), and prolonged survival. This survival trend was more remarkable in cases with matured TLSs, which represented an increased population of CD138+ plasma cells. In the second EC cohort, TLS density predicted the clinical response to anti-PD-1 antibody and patient survival.

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