Abstract 241P
Background
The tumor microenvironment (TIME) directly determines patients' therapeutic efficiencies and clinical outcomes. An in-depth and systemic understanding of the TIME is required to improve the prognosis of patients with gastrointestinal stromal tumor (GIST).
Methods
This study conducted single-cell RNA sequencing of eight-paired tumors and adjacent normal tissues to map the GIST immune landscape, and validated in two independent cohorts [cohort-ZSFD (n=65) and cohort- GSE136755 (n=65)] from the largest sarcoma research center of East China and GEO database, respectively.
Results
T cells, NK cells, B cells and macrophages were highly enriched in the tumor area and transitioned from cytotoxic to exhaustion phenotypes. This study also revealed tumor- specific germinal center B (GC-B) cells associated with tertiary lymphoid structure (TLS). Imatinib sensitive GIST was identified by enriched B cell signature, especially with the IgA+ plasma cell (PC) signature, while the resistant group enriched with cancer related fibroblast (CAF) signature. IgG+ PC had a high potential to extensively interact with SPP1+ TAMs through a significantly enriched ligand-receptor pair in CCL2-CCR2. Combined with transcriptome data, the GIST immune classes (GICs: A-C) was constructed by eight immune cell types and two stroma components through ssGSEA method. A high proportion of GC-B cell and IgG+PC, as well as GIC-C in GIST was predictive of favorable clinical outcomes and associated with elevated hormonal immune responses.
Conclusions
Our study depicts an immune-excluded stromal landscape of TIME ecosystem, and offers valuable insights for its connection with antitumor response and paves the way for potential markers of efficacy evaluation and imatinib resistance in GIST.
Legal entity responsible for the study
H. Tong.
Funding
National Natural Science Foundation of China (81802302); Scientific Research Project of Shanghai Municipal Health Commission (20214Y0087, 20204Y0409); Hongkou District Clinical Medicine Outstanding Young Talents Training Program (No. HKLCYQ2024-01); "Young Talents" Training Plan of Shanghai TCM-integrated Hospital (No. RCPY0063); Scientific Research Project of Shanghai TCM-integrated Hospital (No. 18-01-03); Scientific Research Project of Hongkou District Health Committee (No. 2302-02, No. 2003-02); Natural Science Foundation of Fujian province (No. 2023J011698); Natural Science Foundation of Xiamen City (No. 3502Z20227279).
Disclosure
All authors have declared no conflicts of interest.