Spatial heterogeneity of infiltrating T cells in high-grade serous ovarian cancer revealed by multi-omics analysis

Bin Yang; Xiong Li; Wei Zhang; Junpeng Fan; Yong Zhou; Wenting Li; Jingjing Yin; Xiaohang Yang; Ensong Guo; Xi Li; Yu Fu; Si Liu; Dianxing Hu; Xu Qin; Yingyu Dou; Rourou Xiao; Funian Lu; Zizhuo Wang; Tianyu Qin; Wei Wang; Qinghua Zhang; Shuaicheng Li; Ding Ma; Gordon B. Mills; Gang Chen; Chaoyang Sun

doi:10.1016/j.xcrm.2022.100856

Spatial heterogeneity of infiltrating T cells in high-grade serous ovarian cancer revealed by multi-omics analysis

Bin Yang, Xiong Li, Wei Zhang, Junpeng Fan, Yong Zhou, Wenting Li, Jingjing Yin, Xiaohang Yang, Ensong Guo, Xi Li, Yu Fu, Si Liu, Dianxing Hu, Xu Qin, Yingyu Dou, Rourou Xiao, Funian Lu, Zizhuo Wang, Tianyu Qin, Wei WangQinghua Zhang, Shuaicheng Li, Ding Ma, Gordon B. Mills, Gang Chen, Chaoyang Sun

Cell Developmental and Cancer Biology

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

Abstract

Tumor-infiltrating lymphocytes (TILs), especially CD8⁺ TILs, represent a favorable prognostic factor in high-grade serous ovarian cancer (HGSOC) and other tumor lineages. Here, we analyze the spatial heterogeneity of different TIL subtypes in HGSOC. We integrated RNA sequencing, whole-genome sequencing, bulk T cell receptor (TCR) sequencing, as well as single-cell RNA/TCR sequencing to investigate the characteristics and differential composition of TILs across different HGSOC sites. Two immune “cold” patterns in ovarian cancer are identified: (1) ovarian lesions with low infiltration of mainly dysfunctional T cells and immunosuppressive Treg cells and (2) omental lesions infiltrated with non-tumor-specific bystander cells. Exhausted CD8 T cells that are preferentially enriched in ovarian tumors exhibit evidence for expansion and cytotoxic activity. Inherent tumor immune microenvironment characteristics appear to be the main contributor to the spatial differences in TIL status. The landscape of spatial heterogeneity of TILs may inform potential strategies for therapeutic manipulation in HGSOC.

Original language	English (US)
Article number	100856
Journal	Cell Reports Medicine
Volume	3
Issue number	12
DOIs	https://doi.org/10.1016/j.xcrm.2022.100856
State	Published - Dec 20 2022

Keywords

TILs
high-grade serous ovarian cancer
multi-omics
multiple lesions
spatial heterogeneity

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.xcrm.2022.100856

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Yang, B., Li, X., Zhang, W., Fan, J., Zhou, Y., Li, W., Yin, J., Yang, X., Guo, E., Li, X., Fu, Y., Liu, S., Hu, D., Qin, X., Dou, Y., Xiao, R., Lu, F., Wang, Z., Qin, T., ... Sun, C. (2022). Spatial heterogeneity of infiltrating T cells in high-grade serous ovarian cancer revealed by multi-omics analysis. Cell Reports Medicine, 3(12), Article 100856. https://doi.org/10.1016/j.xcrm.2022.100856

Yang, B, Li, X, Zhang, W, Fan, J, Zhou, Y, Li, W, Yin, J, Yang, X, Guo, E, Li, X, Fu, Y, Liu, S, Hu, D, Qin, X, Dou, Y, Xiao, R, Lu, F, Wang, Z, Qin, T, Wang, W, Zhang, Q, Li, S, Ma, D, Mills, GB, Chen, G & Sun, C 2022, 'Spatial heterogeneity of infiltrating T cells in high-grade serous ovarian cancer revealed by multi-omics analysis', Cell Reports Medicine, vol. 3, no. 12, 100856. https://doi.org/10.1016/j.xcrm.2022.100856

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title = "Spatial heterogeneity of infiltrating T cells in high-grade serous ovarian cancer revealed by multi-omics analysis",

abstract = "Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, represent a favorable prognostic factor in high-grade serous ovarian cancer (HGSOC) and other tumor lineages. Here, we analyze the spatial heterogeneity of different TIL subtypes in HGSOC. We integrated RNA sequencing, whole-genome sequencing, bulk T cell receptor (TCR) sequencing, as well as single-cell RNA/TCR sequencing to investigate the characteristics and differential composition of TILs across different HGSOC sites. Two immune “cold” patterns in ovarian cancer are identified: (1) ovarian lesions with low infiltration of mainly dysfunctional T cells and immunosuppressive Treg cells and (2) omental lesions infiltrated with non-tumor-specific bystander cells. Exhausted CD8 T cells that are preferentially enriched in ovarian tumors exhibit evidence for expansion and cytotoxic activity. Inherent tumor immune microenvironment characteristics appear to be the main contributor to the spatial differences in TIL status. The landscape of spatial heterogeneity of TILs may inform potential strategies for therapeutic manipulation in HGSOC.",

keywords = "TILs, high-grade serous ovarian cancer, multi-omics, multiple lesions, spatial heterogeneity",

author = "Bin Yang and Xiong Li and Wei Zhang and Junpeng Fan and Yong Zhou and Wenting Li and Jingjing Yin and Xiaohang Yang and Ensong Guo and Xi Li and Yu Fu and Si Liu and Dianxing Hu and Xu Qin and Yingyu Dou and Rourou Xiao and Funian Lu and Zizhuo Wang and Tianyu Qin and Wei Wang and Qinghua Zhang and Shuaicheng Li and Ding Ma and Mills, {Gordon B.} and Gang Chen and Chaoyang Sun",

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doi = "10.1016/j.xcrm.2022.100856",

language = "English (US)",

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T1 - Spatial heterogeneity of infiltrating T cells in high-grade serous ovarian cancer revealed by multi-omics analysis

AU - Yang, Bin

AU - Li, Xiong

AU - Zhang, Wei

AU - Fan, Junpeng

AU - Zhou, Yong

AU - Li, Wenting

AU - Yin, Jingjing

AU - Yang, Xiaohang

AU - Guo, Ensong

AU - Li, Xi

AU - Fu, Yu

AU - Liu, Si

AU - Hu, Dianxing

AU - Qin, Xu

AU - Dou, Yingyu

AU - Xiao, Rourou

AU - Lu, Funian

AU - Wang, Zizhuo

AU - Qin, Tianyu

AU - Wang, Wei

AU - Zhang, Qinghua

AU - Li, Shuaicheng

AU - Ma, Ding

AU - Mills, Gordon B.

AU - Chen, Gang

AU - Sun, Chaoyang

PY - 2022/12/20

Y1 - 2022/12/20

N2 - Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, represent a favorable prognostic factor in high-grade serous ovarian cancer (HGSOC) and other tumor lineages. Here, we analyze the spatial heterogeneity of different TIL subtypes in HGSOC. We integrated RNA sequencing, whole-genome sequencing, bulk T cell receptor (TCR) sequencing, as well as single-cell RNA/TCR sequencing to investigate the characteristics and differential composition of TILs across different HGSOC sites. Two immune “cold” patterns in ovarian cancer are identified: (1) ovarian lesions with low infiltration of mainly dysfunctional T cells and immunosuppressive Treg cells and (2) omental lesions infiltrated with non-tumor-specific bystander cells. Exhausted CD8 T cells that are preferentially enriched in ovarian tumors exhibit evidence for expansion and cytotoxic activity. Inherent tumor immune microenvironment characteristics appear to be the main contributor to the spatial differences in TIL status. The landscape of spatial heterogeneity of TILs may inform potential strategies for therapeutic manipulation in HGSOC.

AB - Tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, represent a favorable prognostic factor in high-grade serous ovarian cancer (HGSOC) and other tumor lineages. Here, we analyze the spatial heterogeneity of different TIL subtypes in HGSOC. We integrated RNA sequencing, whole-genome sequencing, bulk T cell receptor (TCR) sequencing, as well as single-cell RNA/TCR sequencing to investigate the characteristics and differential composition of TILs across different HGSOC sites. Two immune “cold” patterns in ovarian cancer are identified: (1) ovarian lesions with low infiltration of mainly dysfunctional T cells and immunosuppressive Treg cells and (2) omental lesions infiltrated with non-tumor-specific bystander cells. Exhausted CD8 T cells that are preferentially enriched in ovarian tumors exhibit evidence for expansion and cytotoxic activity. Inherent tumor immune microenvironment characteristics appear to be the main contributor to the spatial differences in TIL status. The landscape of spatial heterogeneity of TILs may inform potential strategies for therapeutic manipulation in HGSOC.

KW - TILs

KW - high-grade serous ovarian cancer

KW - multi-omics

KW - multiple lesions

KW - spatial heterogeneity

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Spatial heterogeneity of infiltrating T cells in high-grade serous ovarian cancer revealed by multi-omics analysis

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Keywords

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