Cancer; Gastroenterology; Humans; RNA-Seq/methods; Single-Cell Analysis/methods; Transcriptome/genetics; Colorectal Neoplasms/classification; Colorectal Neoplasms/genetics; Colorectal Neoplasms/metabolism; Colorectal Neoplasms/pathology; Colorectal Neoplasms; RNA-Seq; Single-Cell Analysis; Transcriptome; Medicine (all); General Medicine
Abstract :
[en] Colorectal cancers (CRCs) exhibit differences in incidence, pathogenesis, molecular pathways, and outcome depending on the location of the tumor. The transcriptomes of 27,927 single human CRC cells from 3 left-sided and 3 right-sided CRC patients were profiled by single-cell RNA-Seq (scRNA-Seq). Right-sided CRC harbors a significant proportion of exhausted CD8+ T cells of a highly migratory nature. One cluster of cells from left-sided CRC exhibiting states preceding exhaustion and a high ratio of preexhausted/exhausted T cells were favorable prognostic markers. Notably, we identified a potentially novel RBP4+NTS+ subpopulation of cancer cells that exclusively expands in left-sided CRC. Tregs from left-sided CRC showed higher levels of immunotherapy-related genes than those from right-sided CRC, indicating that left-sided CRC may have increased responsiveness to immunotherapy. Antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) induced by M2-like macrophages were more pronounced in left-sided CRC and correlated with a good prognosis in CRC.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Guo, Wei; Department of Colorectal Surgery, Shandong University Qilu Hospital, Jinan, Shandong, China
Zhang, Cuiyu; Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
Wang, Xia; Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
Dou, Dandan; Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
NSCF - National Natural Science Foundation of China
Funding text :
This work was supported by the National Natural Science Foundation of China (82000779, 31971061) and Taishan Pandeng Scholar Program of Shandong Province (tspd20210321).
Venook AP, et al. CALGB/SWOG 80405: Phase III trial of irinotecan/5-FU/leucovorin (FOLFIRI) or oxaliplatin/5-FU/leucovorin (mFOLFOX6) with bevacizumab (RV) or cetuximab (CET) for patients (pts) with KRAS wild-type (wt) untreated metastatic adenocarcinoma of the colon or rectum (MCRC). Paper presented at: 2014 Annual Meeting of the American Society of Clinical Oncology; May 30-June 3, 2014; Chicago, Illinois, USA. https://meetinglibrary.asco.org/record/94399/abstract. Accessed November 23, 2021.
Hong TS, et al. Cancers of the colon and rectum: Identical or fraternal twins? Cancer Discov. 2012; 2(2):117-121.
Bufill JA. Colorectal-cancer - evidence for distinct genetic categories based on proximal or distal tumor location. Ann Intern Med. 1990; 113(10):779-788.
Distler P, Holt PR. Are right- and left-sided colon neoplasms distinct tumors? Dig Dis. 1997; 15(4-5):302-311.
Hutchins G, et al. Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol. 2011; 29(10):1261-1270.
Birkenkamp-Demtroder K, et al. Differential gene expression in colon cancer of the caecum versus the sigmoid and rectosigmoid. Gut. 2005; 54(3):374-384.
Gerlinger M, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med. 2012; 366(10):883-892.
Guo XY, et al. Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing. Nat Med. 2018; 24(7):978-985.
Su SC, et al. Blocking the recruitment of naive CD4+ T cells reverses immunosuppression in breast cancer. Cell Res. 2017; 27(4):461-482.
Danaher P, et al. Gene expression markers of tumor infiltrating leukocytes. J Immunother Cancer. 2017; 5:18.
Tirosh I, et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science. 2016; 352(6282):189-196.
Mueller SN, et al. Memory T cell subsets, migration patterns, and tissue residence. Annu Rev Immunol. 2013; 31:137-161.
Zitvogel L, et al. Following up tumor-specific regulatory T cells in cancer patients. Oncoimmunology. 2013; 2(7):e25444.
Nishikawa H, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Curr Opin Immunol. 2014; 27:1-7.
Curiel TJ, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004; 10(9):942-949.
Facciabene A, et al. Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature. 2011; 475(7355):226-230.
Plitas G, et al. Regulatory T cells exhibit distinct features in human breast cancer. Immunity. 2016; 45(5):1122-1134.
Savage PA, et al. Shaping the repertoire of tumor-infiltrating effector and regulatory T cells. Immunol Rev. 2014; 259(1):245-258.
Belkaid Y, Oldenhove G. Tuning microenvironments: Induction of regulatory T cells by dendritic cells. Immunity. 2008; 29(3):362-371.
Wei S, et al. Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade. Cell. 2017; 5(6):1120-1133.
Pelaseyed T, et al. The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system. Immunol Rev. 2014; 260(1):8-20.
Vandenbroucke K, et al. Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice. Gastroenterology. 2004; 127(2):502-513.
Manca S, et al. The role of alcohol-induced Golgi fragmentation for androgen receptor signaling in prostate cancer. Mol Cancer Res. 2019; 17(1):225-237.
Li XF, et al. CLCA1 suppresses colorectal cancer aggressiveness via inhibition of the Wnt/beta-catenin signaling pathway. Cell Commun Signal. 2017; 15(1):38.
Williams C, et al. Estrogen receptor beta as target for colorectal cancer prevention. Cancer Lett. 2016; 372(1):48-56.
Greally M, et al. HER2: An emerging target in colorectal cancer. Curr Probl Cancer. 2018; 42(6):560-571.
Koehler BC, et al. Targeting cell death signaling in colorectal cancer: Current strategies and future perspectives. World J Gastroenterol. 2014; 20(8):1923-1934.
Wong SHM, et al. The TRAIL to cancer therapy: Hindrances and potential solutions. Crit Rev Oncol Hematol. 2019; 143:81-94.
Li FZ, et al. TGF-beta signaling in colon cancer cells. World J Surg. 2005; 29(3):306-311.
Zigmond E, et al. Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells. Immunity. 2012; 37(6):1076-1090.
Morias Y, et al. Ly6C- Monocytes regulate parasite-induced liver inflammation by inducing the differentiation of pathogenic Ly6C+ monocytes into macrophages. PLoS Pathog. 2015; 11(5):e1004873.
Shechter R, et al. Recruitment of beneficial M2 macrophages to injured spinal cord is orchestrated by remote brain choroid plexus. Immunity. 2013; 38(3):555-569.
Mantovani A, et al. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol. 2017; 14(7):399-416.
Li ZH, et al. N6-methyladenosine regulates glycolysis of cancer cells through PDK4. Nat Commun. 2020; 11(1):2578.
Zhang QM, et al. Landscape and dynamics of single immune cells in hepatocellular carcinoma. Cell. 2019; 179(4):829-845.
Yang H, et al. Stress-glucocorticoid-TSC22D3 axis compromises therapy-induced antitumor immunity. Nat Med. 2019; 25(9):1428-1441.
Gao S, et al. Tracing the temporal-spatial transcriptome landscapes of the human fetal digestive tract using single-cell RNA-sequencing. Nat Cell Biol. 2018; 20(10):1227.
Haber AL, et al. A single-cell survey of the small intestinal epithelium. Nature. 2017; 551(7680):333-339.
Zhang P, Yet al. Dissecting the single-cell transcriptome network underlying gastric premalignant lesions and early gastric cancer. Cell Rep. 2020; 30(12):4317.
Franke AJ, et al. Immunotherapy for colorectal cancer: A review of current and novel therapeutic approaches. J Natl Cancer Inst. 2019; 111(11):1131-1141.
Butler A, et al. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018; 36(5):411-420.
