Journal
ANNALS OF SURGERY
Volume 275, Issue 4, Pages E626-E635Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/SLA.0000000000004037
Keywords
adjuvant chemotherapy; gastric cancer; immune evasion; interleukin-10; macrophages; prognosis
Categories
Funding
- National Natural Science Foundation of China [81671628, 81871306, 81871930, 81902402, 81902901, 81972219]
- Shanghai Sailing Program [17YF1402200, 18YF1404600, 19YF1407500]
Ask authors/readers for more resources
This study revealed the clinical significance of IL-10(+) tumor-associated macrophages (TAMs) in gastric cancer. It showed that high IL-10(+) TAM infiltration was associated with poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy. IL-10(+) TAMs drove an immunoevasive tumor microenvironment, indicating their potential as a target for immunotherapeutic approach in gastric cancer.
Objective: To investigate the clinical significance of IL-10(+) tumor-associated macrophages (TAMs) in gastric cancer. Background: Due to the plasticity and diversity of TAMs, it is necessary to phenotypically and functionally classify subsets of TAMs to better understand the critical role of TAMs in cancer progression. TAMs expressing interleukin-10 (IL-10) have been found to facilitate immune evasion in many malignancies, but the role of IL-10(+) TAMs in gastric cancer remains obscure. Methods: Four hundred and sixty-eight tumor tissue microarray specimens, 52 fresh tumor tissue samples of gastric cancer patients from Zhongshan Hospital, and data of 298 gastric cancer patients from the Cancer Genome Atlas (TCGA) were analyzed. IL-10(+) TAM level and immune contexture were examined by CIBERSORT, immunohistochemistry, and flow cytometry. Clinical outcomes were analyzed by Kaplan-Meier curves and Cox model. Results: Gastric cancer patients with high IL-10(+) TAM infiltration exhibited poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy. IL-10(+) TAM infiltration yielded an immunoevasive tumor microenvironment featured by regulatory T cell infiltration and CD8(+) T cell dysfunction. The combinational analysis of IL-10(+) TAM and CD8(+) T cell infiltration stratified patients into distinct risk groups with different clinical outcomes. Moreover, IL-10(+) TAM infiltration was correlated with tumor-intrinsic characteristics including EBV status, PD-L1 expression, and genome stability in gastric cancer. Conclusions: This study revealed that IL-10(+) TAMs might drive an immunoevasive microenvironment and determine poor prognosis and inferior therapeutic responsiveness to fluorouracil-based adjuvant chemotherapy, indicating IL-10(+) TAMs could be applied as a potential target for immunotherapeutic approach in gastric cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available