Single-cell analysis of immune-microenvironment and immune-tumor interaction in human gastric cancers.

Authors

null

Michele Goh

Singapore Immunology Network, A * STAR, Singapore, Singapore

Michele Goh , Ze Ming Lim , Vivien Koh , Josephine Lum , Xiaomeng Zhang , Naomi McGovern , Rasha Msallam , Anis Larbi , Michael Poidinger , Florent Ginhoux , Matthew C.H. Ng , Patrick Tan , Wei Peng Yong , Jimmy Bok Yan So , Jinmiao Chen

Organizations

Singapore Immunology Network, A * STAR, Singapore, Singapore, Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore, National Cancer Centre Singapore, Singapore, Singapore, Duke-NUS Graduate Medical School, Singapore, Singapore, National University Cancer Institute, Singapore, Singapore, Department of Surgery, National University Health System, Singapore, Singapore, Singapore

Research Funding

Other

Background: The incidence rates of gastric cancer in Asia are among the highest in the world. Gastric cancer is a heterogeneous disease. The Cancer Genome Atlas and Asian Cancer Research Group provide molecular classification of gastric cancers. Recently, immunotherapy was found to be effective in selected gastric cancer patients. Despite the molecular classification, a classification system based on immune microenvironment is in need to better stratify patients for ideal immunotherapy combinations. Methods: We have performed indexed-sorting single cell RNA-seq to analyze both CD45+ and CD45- cells from biopsy samples of 15 gastric cancer patients (5 Diffuse; 4 Intestinal; 5 Mixed; 1 unknown type). Using our ezsinglecell analytical pipeline, we have built a draft Asian Single-cell Immune Atlas (ASIA) of human gastric cancers. Results: We were able to probe fibroblast, epithelial cells and various subtypes of immune cells. Interestingly, we observed that fibroblast and mast cells were more enriched in diffuse type. In addition, we have profiled single immune cells in tumor and normal adjacent tissues to distinguish tissue-induced versus tumor-driven immune signatures. Comparing tumor and normal tissues, we found that tumor site has less natural killer (NK) and CD8 T cells; more B, myeloid and CD4 T cells. Moreover, CD8 T cells and NK cells showed distinct phenotypes in tumor compared to normal tissues. In particular, inhibitory receptor Tim-3 and CTLA-4 were up-regulated in the tumor. Most interestingly, T Cell Receptor (TCR) reconstruction revealed clonal expansion of CD8 T cells. Conclusions: Both immune (CD45+) and non-immune (CD45-) cell components of human gastric cancers are highly heterogeneous. Diffuse type showed differential tumor microenvironment compared to intestinal and mixed types. Tumor site presented an immune-suppressive phenotype compared to normal adjacent site. The clonal expansion of CD8 T cells suggested the role of adaptive immunity on recognizing tumor antigens. This discovery may determine the clinical applications of immunotherapy for gastric cancer in the future.

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Abstract Details

Meeting

2019 Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Cancers of the Esophagus and Stomach

Track

Cancers of the Esophagus and Stomach

Sub Track

Prevention, Diagnosis, and Screening

Citation

J Clin Oncol 37, 2019 (suppl 4; abstr 29)

DOI

10.1200/JCO.2019.37.4_suppl.29

Abstract #

29

Poster Bd #

E19

Abstract Disclosures

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