Tumor-infiltrating T Cells As a Risk Factor for Lymph Node Metastasis in Patients with Submucosal Colorectal Cancer

Overview

Journal Sci Rep

Specialty Science

Date 2023 Feb 6

PMID 36746991

Authors

Masatoshi Kitakaze

Shiki Fujino

Norikatsu Miyoshi

Yuki Sekido

Tsuyoshi Hata

Takayuki Ogino

Hidekazu Takahashi

Mamoru Uemura

Tsunekazu Mizushima

Yuichiro Doki

Hidetoshi Eguchi

Affiliations

Soon will be listed here.

Abstract

Approximately 10% of patients with colorectal cancer with submucosal invasion have lymph node metastasis. Pathological risk factors for lymph node metastasis have varying sensitivities and specificities. To predict the risk of lymph node metastasis, the identification of new risk factors is vital. Tumor-infiltrating T cells have been reported to improve the prognosis of many solid tumors. Therefore, the purpose of this study was to examine the relationship between lymph node metastasis and tumor-infiltrating T cells in patients with colorectal cancer with submucosal invasion. We examined CD8 tumor-infiltrating T cells level as a risk factor for lymph node metastasis in patients with colorectal cancer with submucosal invasion. Using immunohistochemical staining, we identified CD8 + T cells in surgically resected specimens from 98 patients with SM-CRC. We showed that low CD8 tumor-infiltrating T cells levels are positively correlated with lymph node metastasis. Furthermore, by combining the number of CD8 tumor-infiltrating T cell and the number of CD103 tumor-infiltrating T cells, the results showed a high positive predictive value for lymph node metastasis in cases with low numbers of both types of tumor-infiltrating T cells and a high negative predictive value in cases with high numbers of both types of tumor-infiltrating T cells.

Citing Articles

Prognostic Value of Combined LMR and CEA Dynamic Monitoring in Postoperative Colorectal Cancer Patients.

Chen S, Zhang J, Qian C, Qi X, Mao Y, Lu T J Inflamm Res. 2023; 16:4229-4250.

PMID: 37772275 PMC: 10522459. DOI: 10.2147/JIR.S422500.

References

Amsen D, van Gisbergen K, Hombrink P, van Lier R . Tissue-resident memory T cells at the center of immunity to solid tumors. Nat Immunol. 2018; 19(6):538-546. DOI: 10.1038/s41590-018-0114-2. View

Wong S, Fang C, Chuah L, Leong C, Ching Ngai S . E-cadherin: Its dysregulation in carcinogenesis and clinical implications. Crit Rev Oncol Hematol. 2017; 121:11-22. DOI: 10.1016/j.critrevonc.2017.11.010. View

Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C . Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006; 313(5795):1960-4. DOI: 10.1126/science.1129139. View

Jou J, Diehl A . Epithelial-mesenchymal transitions and hepatocarcinogenesis. J Clin Invest. 2010; 120(4):1031-4. PMC: 2846072. DOI: 10.1172/JCI42615. View

Takada K, Kashiwagi S, Asano Y, Goto W, Kouhashi R, Yabumoto A . Prediction of lymph node metastasis by tumor-infiltrating lymphocytes in T1 breast cancer. BMC Cancer. 2020; 20(1):598. PMC: 7318528. DOI: 10.1186/s12885-020-07101-y. View

Wang B, Wu S, Zeng H, Liu Z, Dong W, He W . CD103+ Tumor Infiltrating Lymphocytes Predict a Favorable Prognosis in Urothelial Cell Carcinoma of the Bladder. J Urol. 2015; 194(2):556-62. DOI: 10.1016/j.juro.2015.02.2941. View

Fridman W, Pages F, Sautes-Fridman C, Galon J . The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012; 12(4):298-306. DOI: 10.1038/nrc3245. View

Beaton C, Twine C, Williams G, Radcliffe A . Systematic review and meta-analysis of histopathological factors influencing the risk of lymph node metastasis in early colorectal cancer. Colorectal Dis. 2013; 15(7):788-97. DOI: 10.1111/codi.12129. View

Ueno H, Hase K, Hashiguchi Y, Shimazaki H, Yoshii S, Kudo S . Novel risk factors for lymph node metastasis in early invasive colorectal cancer: a multi-institution pathology review. J Gastroenterol. 2013; 49(9):1314-23. DOI: 10.1007/s00535-013-0881-3. View

10.

Barnes T, Amir E . HYPE or HOPE: the prognostic value of infiltrating immune cells in cancer. Br J Cancer. 2017; 117(4):451-460. PMC: 5558691. DOI: 10.1038/bjc.2017.220. View

11.

Chen Z, Zhang C, Pan Y, Xu R, Xu C, Chen Z . T cell receptor β-chain repertoire analysis reveals intratumour heterogeneity of tumour-infiltrating lymphocytes in oesophageal squamous cell carcinoma. J Pathol. 2016; 239(4):450-8. DOI: 10.1002/path.4742. View

12.

Min B, Yang J, Min Y, Baek S, Kim S, Kim H . Nomogram for prediction of lymph node metastasis in patients with superficial esophageal squamous cell carcinoma. J Gastroenterol Hepatol. 2019; 35(6):1009-1015. DOI: 10.1111/jgh.14915. View

13.

Ling K, Dulphy N, Bahl P, Salio M, Maskell K, Piris J . Modulation of CD103 expression on human colon carcinoma-specific CTL. J Immunol. 2007; 178(5):2908-15. DOI: 10.4049/jimmunol.178.5.2908. View

14.

Ohue Y, Nishikawa H . Regulatory T (Treg) cells in cancer: Can Treg cells be a new therapeutic target?. Cancer Sci. 2019; 110(7):2080-2089. PMC: 6609813. DOI: 10.1111/cas.14069. View

15.

Caro G, Bergomas F, Grizzi F, Doni A, Bianchi P, Malesci A . Occurrence of tertiary lymphoid tissue is associated with T-cell infiltration and predicts better prognosis in early-stage colorectal cancers. Clin Cancer Res. 2014; 20(8):2147-58. DOI: 10.1158/1078-0432.CCR-13-2590. View

16.

Hendry S, Salgado R, Gevaert T, Russell P, John T, Thapa B . Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract.... Adv Anat Pathol. 2017; 24(6):311-335. PMC: 5638696. DOI: 10.1097/PAP.0000000000000161. View

17.

Gorfu G, Rivera-Nieves J, Ley K . Role of beta7 integrins in intestinal lymphocyte homing and retention. Curr Mol Med. 2009; 9(7):836-50. PMC: 2770881. DOI: 10.2174/156652409789105525. View

18.

Hashiguchi Y, Muro K, Saito Y, Ito Y, Ajioka Y, Hamaguchi T . Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2019; 25(1):1-42. PMC: 6946738. DOI: 10.1007/s10147-019-01485-z. View

19.

Sheu B, Kuo W, Chen R, Huang S, Chang K, Chow S . Clinical significance of tumor-infiltrating lymphocytes in neoplastic progression and lymph node metastasis of human breast cancer. Breast. 2008; 17(6):604-10. DOI: 10.1016/j.breast.2008.06.001. View

20.

Sakaguchi S . Regulatory T cells: key controllers of immunologic self-tolerance. Cell. 2000; 101(5):455-8. DOI: 10.1016/s0092-8674(00)80856-9. View