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The Immune Microenvironment Impacts Survival in Western Patients with Gastric Adenocarcinoma

  • 2019 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Background

Expression of CD3+ T cells, CD8+ cytotoxic T cells, CD45RO+ memory T cells, and FOXP3+ regulatory T cells at the invasive margin (IM) and tumor center (TC) has correlated with survival in gastric adenocarcinoma (GA) patients from East Asia, independent of anatomic staging. The reason for improved survival in East Asians compared with Western patients is a subject of debate. This study examined the immune profiles of a cohort of Western patients with GA, and their association with overall survival (OS).

Methods

Immunohistochemistry (IHC) using antibodies to CD3, CD4, CD8, CD45RO, and FOXP3 was performed on a randomly selected resected GA specimens from 88 Western patients. Cutoffs for high or low expression of each marker were determined with maximally selected rank statistics, and multivariable Cox proportional-hazards models constructed to evaluate the relationship between OS and expression of each marker at the IM and TC.

Results

Immune cell density was independent of anatomic staging. High expression of CD3, CD4, CD8, and CD45RO at the IM along with CD4 and FOXP3 at the TC were associated with improved OS. A combined marker of CD3, CD8, CD45RO, and FOXP3 associated with OS in East Asian GA was also validated.

Discussion

This is the first report in US patients to demonstrate that high expression of multiple subsets of T lymphocytes in GA is associated with better OS independent of clinical factors and anatomic stage. Further evaluation of immune-modulating mechanisms may explain survival differences between Western and Eastern patients and provide opportunity for novel treatments.

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Abbreviations

GA:

Gastric adenocarcinoma

TIL:

Tumor-infiltrating lymphocyte

IHC:

Immunohistochemistry

OS:

Overall survival

IM:

Invasive margin

TC:

Tumor center

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Funding

This study was funded by the Gastrointestinal Research Program, John Wayne Cancer Institute.

Author information

Authors and Affiliations

  1. Department of Surgical Oncology, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA, 90404, USA

    Abhineet Uppal, Ahmed Dehal & Anton J. Bilchik

  2. Medical Data Research Center, Providence St. Joseph Health, Portland, OR, USA

    Shu-Ching Chang

  3. Department of Surgery, Georgetown University Hospital, Washington, DC, USA

    Dany Barrak

  4. Department of Pathology, Providence St. John’s Medical Center, Santa Monica, CA, USA

    Yalda Naeini & John R. Jalas

Authors
  1. Abhineet Uppal
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  2. Ahmed Dehal
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Contributions

All authors contributed to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. AU drafted the work, and all other authors revised it critically for content. All authors approve the manuscript.

Corresponding author

Correspondence to Anton J. Bilchik.

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This study was presented as a Plenary at the 2019 Society for the Surgery of the Alimentary Tract, San Diego, CA, May 21, 2019.

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Uppal, A., Dehal, A., Chang, SC. et al. The Immune Microenvironment Impacts Survival in Western Patients with Gastric Adenocarcinoma. J Gastrointest Surg 24, 28–38 (2020). https://doi.org/10.1007/s11605-019-04403-w

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  • DOI: https://doi.org/10.1007/s11605-019-04403-w

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