The Immune Microenvironment Impacts Survival in Western Patients with Gastric Adenocarcinoma.

Publication Title

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract

Authors

Abhineet Uppal, John Wayne Cancer Institute at Providence Saint John's Hospital, Santa Monica, CAFollow
Ahmed N Dehal, John Wayne Cancer Institute at Providence St John's Health Center, 2200 Santa Monica Blvd, Santa Monica, CA, 90404, USAFollow
Shu-Ching Chang, Medical Data Research Center, Providence Health & Services, Portland, OR, USAFollow
Dany Barrak
Yalda Naeini, Department of Pathology, Providence St. John's Medical Center, Santa Monica, CA, USAFollow
John R Jalas, Department of Pathology, Providence Saint John's Health Center, Santa Monica, CA, USAFollow
Anton J Bilchik, John Wayne Cancer Institute at Providence St John's Health Center, 2200 Santa Monica Blvd, Santa Monica, CA, 90404, USAFollow

Document Type

Article

Publication Date

10-17-2019

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.

Clinical Institute

Cancer

Clinical Institute

Digestive Health

Specialty/Research Institute

Oncology

Specialty/Research Institute

Gastroenterology