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

Br J Cancer. 2023 Jun;128(12):2175-2185. doi: 10.1038/s41416-023-02235-9. Epub 2023 Apr 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Esophageal Neoplasms* / drug therapy
  • Esophageal Squamous Cell Carcinoma* / drug therapy
  • Humans
  • Immune Checkpoint Inhibitors
  • Prognosis
  • Tertiary Lymphoid Structures* / metabolism
  • Tumor Microenvironment

Substances

  • Immune Checkpoint Inhibitors