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Background <p>Tumour infiltrating lymphocytes (TILs) are a key component of the tumour microenvironment. To establish a clinically relevant TILs cut-off for patients with oesophago-gastric (OG) cancer, it is essential to know whether TILs density varies by patient and/or disease characteristics.</p> Materials and methods <p>TILs were quantified as TILs/mm<sup>2</sup> (TILs density) by a deep-learning algorithm applied to digitised Haematoxylin/Eosin (H&amp;E)-stained biopsies and resection specimens from 4628 patients from nine phase III trials. 4533 patients with TILs density and matched clinicopathological data were included in the final analyses. Associations between TILs density, disease stage, geographical region (UK versus Asia), sex, age, and treatment were analysed.</p> Results <p>Median TILs density was higher in pre-treatment biopsies from patients with early-stage versus late-stage disease (962 vs 479 TILs/mm<sup>2</sup>, <i>p</i> &lt; 0.001). Within the same geographical region and disease stage, TILs density was similar across different chemotherapy regimens. In UK-led trials of early-stage disease, post-chemotherapy resections showed higher TILs density than chemotherapy-naïve resections (618 vs 571 TILs/mm<sup>2</sup>, <i>p</i> = 0.003). TILs density was higher in Asian tumours compared to UK tumours (1419 vs 571 TILs/mm<sup>2</sup>, <i>p</i> &lt; 0.001). No significant associations were observed with age or sex.</p> Conclusions <p>This is the largest study to date evaluating TILs density in OG cancer. TILs density varied with stage and geographical region but not by age or sex. These findings may explain enhanced response to immunotherapy observed in published studies of patients with early-stage disease and highlight the need to account for baseline TILs heterogeneity when interpreting TILs as a possible biomarker in future studies.</p>

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The density of tumour infiltrating lymphocytes in oesophago-gastric cancer varies with disease stage, geographical region and treatment: a post hoc analysis of nine phase III clinical trials

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月5日

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  • Georgina A. Keogh,
  • Nina Šefčovičová,
  • Tomio Arai,
  • Myeong-Cherl Kook,
  • Jon P. Laye,
  • William H. Allum,
  • Sameira Arif,
  • Avani Athauda,
  • Hee Kyung Chang,
  • Jae-Ho Cheong,
  • Mee-Yon Cho,
  • David Cunningham,
  • Lara Heij,
  • Andrew F. Irvine,
  • Hee Sung Kim,
  • Hyunki Kim,
  • Young-Woo Kim,
  • Ruth E. Langley,
  • Sung Hak Lee,
  • Katharina von Loga,
  • Matthew G. Nankivell,
  • Takashi Oshima,
  • Russell D. Petty,
  • Xiuxiang Tan,
  • Shiro Tanaka,
  • Akira Tsuburaya,
  • Judith de Vos-Geelen,
  • Nicholas P. West,
  • Jake Emmerson,
  • Jamie R. Stokes,
  • Derek R. Magee,
  • David A. Cairns,
  • Heike I. Grabsch

摘要

Background

Tumour infiltrating lymphocytes (TILs) are a key component of the tumour microenvironment. To establish a clinically relevant TILs cut-off for patients with oesophago-gastric (OG) cancer, it is essential to know whether TILs density varies by patient and/or disease characteristics.

Materials and methods

TILs were quantified as TILs/mm2 (TILs density) by a deep-learning algorithm applied to digitised Haematoxylin/Eosin (H&E)-stained biopsies and resection specimens from 4628 patients from nine phase III trials. 4533 patients with TILs density and matched clinicopathological data were included in the final analyses. Associations between TILs density, disease stage, geographical region (UK versus Asia), sex, age, and treatment were analysed.

Results

Median TILs density was higher in pre-treatment biopsies from patients with early-stage versus late-stage disease (962 vs 479 TILs/mm2, p < 0.001). Within the same geographical region and disease stage, TILs density was similar across different chemotherapy regimens. In UK-led trials of early-stage disease, post-chemotherapy resections showed higher TILs density than chemotherapy-naïve resections (618 vs 571 TILs/mm2, p = 0.003). TILs density was higher in Asian tumours compared to UK tumours (1419 vs 571 TILs/mm2, p < 0.001). No significant associations were observed with age or sex.

Conclusions

This is the largest study to date evaluating TILs density in OG cancer. TILs density varied with stage and geographical region but not by age or sex. These findings may explain enhanced response to immunotherapy observed in published studies of patients with early-stage disease and highlight the need to account for baseline TILs heterogeneity when interpreting TILs as a possible biomarker in future studies.