SEARCHCOHORToncology, gastroenterology

cohort·oncology, gastroenterology, immunology, surgery, clinical trial·PMC10241865

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

British Journal of Cancer · 19 authors, 6 centres

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TL;DR

This retrospective study evaluated peritumoral tertiary lymphoid structures (TLSs) in oesophageal cancer and found that high density and maturity of TLSs were associated with prolonged survival and a better clinical response to anti-PD-1 antibody treatment in recurrent disease.

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This retrospective study analyzed 316 surgical specimens of oesophageal squamous cell carcinoma from two institutes to evaluate the density and maturity of peritumoral tertiary lymphoid structures (TLSs). High TLS density was associated with less advanced tumour stage, absence of lymphatic/vascular invasion, better nutritional parameters, and prolonged survival, with the survival benefit being more pronounced in cases with mature TLSs containing abundant CD138+ plasma cells. In a separate cohort of 34 patients with recurrent disease, high TLS density in the primary tumour predicted a clinical response to subsequent anti-PD-1 antibody therapy and improved survival. Limitations include the retrospective design and the evaluation of only a single slide per case. The findings suggest that TLS evaluation could serve as a biomarker for prognosis and for predicting response to immunotherapy in oesophageal cancer.

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cohort

SPECIALTY

oncology

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ORIGINAL PAPER

PMC10241865

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

British Journal of Cancer

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ABSTRACT

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). 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. 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.

CITATION EXPORT

Yoshinori Hayashi, Tomoki Makino, Eiichi Sato et al.. Density and maturity of peritumoral tertiary lymphoid structures in oesophageal squamous cell carcinoma predicts patient survival and response to immune checkpoint inhibitors. British Journal of Cancer. (2023). https://doi.org/10.1038/s41416-023-02235-9

AUTHORS

19 · 6 CENTRES

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, Yuichiro Doki

1grid.136593.b0000 0004 0373 3971Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
2grid.136593.b0000 0004 0373 3971Department of Clinical Research in Tumor Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
3grid.410793.80000 0001 0663 3325Department of Pathology, Institute of Medical Science (Medical Research Center), Tokyo Medical University, Tokyo, Japan
4grid.136593.b0000 0004 0373 3971Department of Pathology, Graduate School of Medicine, Osaka University, Osaka, Japan
5grid.489169.b0000 0004 8511 4444Department of Gastroenterological Surgery, Osaka International Cancer Institute, Osaka, Japan
6grid.489169.b0000 0004 8511 4444Department of Pathology, Osaka International Cancer Institute, Osaka, Japan