Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Distribution and Prognostic Significance of T Cell Phenotypes in the Immune Microenvironment of Esophageal Adenocarcinoma and Barrett Esophagus

Isha Khanduri
,
Renganayaki Pandurengan
,
Arlene M Correa
,
Riham Katkhuda
,
Anuj Verma
,
Alicia Mejia
,
Zhimin Tong
,
Akash Mitra
,
Akshaya S Jadhav
,
Luisa M Solis Soto
ORCID logo ,
Ignacio Wistuba
,
Wayne Hofstetter
,
Edwin Roger Parra
ORCID logo ,
Dipen M Maru
*
Version 1 : Received: 13 December 2023 / Approved: 14 December 2023 / Online: 14 December 2023 (06:08:50 CET)

How to cite: Khanduri, I.; Pandurengan, R.; Correa, A.M.; Katkhuda, R.; Verma, A.; Mejia, A.; Tong, Z.; Mitra, A.; Jadhav, A.S.; Solis Soto, L.M.; Wistuba, I.; Hofstetter, W.; Parra, E.R.; Maru, D.M. Distribution and Prognostic Significance of T Cell Phenotypes in the Immune Microenvironment of Esophageal Adenocarcinoma and Barrett Esophagus. Preprints 2023, 2023121053. https://doi.org/10.20944/preprints202312.1053.v1 Khanduri, I.; Pandurengan, R.; Correa, A.M.; Katkhuda, R.; Verma, A.; Mejia, A.; Tong, Z.; Mitra, A.; Jadhav, A.S.; Solis Soto, L.M.; Wistuba, I.; Hofstetter, W.; Parra, E.R.; Maru, D.M. Distribution and Prognostic Significance of T Cell Phenotypes in the Immune Microenvironment of Esophageal Adenocarcinoma and Barrett Esophagus. Preprints 2023, 2023121053. https://doi.org/10.20944/preprints202312.1053.v1

Abstract

The T cell composition of the tumor microenvironment (TME) of esophageal adenocarcinoma (EAC) in comparison to the T cell composition of the TME of Barrett esophagus (BE) and in the context of clinicopathologic features and patient survival is unknown. To help fill these knowledge gaps, we used a multiplex immunofluorescence platform to study adaptive T cells and T cell subtypes based on costimulatory/inhibitory markers in EAC (n=54) and matched BE (n=21) samples from 54 patients with EAC and correlated the T cell phenotype distribution with clinicopathologic features and disease-free survival. We observed significant enrichment of cytotoxic T cells (CTCs), memory T cells, effector memory T cells, memory T regulatory cells (MTregs), and T cells expressing costimulatory/inhibitory markers LAG3, TIM3, and ICOS in EAC compared to BE, in the stroma. In EAC, increased TIM3 expression on T cells significantly correlated with increased CTCs but not T regulatory cells (Tregs). In EAC, higher densities of Tregs and MTregs correlated with pT1 disease, low pathologic stage, and absence of lymphovascular invasion. In EAC, patients with higher density of TIM3-expressing T cells had shorter disease-free survival by univariate and multivariate analyses. Our results identify T cell subtypes that are relevant to EAC biology and patient outcome. Furthermore, our results identify TIM3 as a potential target for optimization of immunomodulatory therapy in EAC.

Keywords

Esophagus; adenocarcinoma; Barrett esophagus; multiplex immunofluorescence; T regulatory cells; TIM3

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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