Significance of tumor-associated neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio in non-invasive and invasive bladder urothelial carcinoma
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Background: Tumor-infiltrating neutrophils and lymphocytes play essential roles in promoting or combating various neoplasms. This study aimed to investigate the association between tumor-infiltrating neutrophils and lymphocytes and the neutrophil-to-lymphocyte ratio in the progression of urothelial carcinoma. Methods: A total of 106 patients diagnosed with urothelial carcinoma were was. Pathological examination for tumor grade and stage and for tumor-infiltrating neutrophils, both CD4 and CD8+ T lymphocytes, as well as the neutrophil- to-lymphocyte ratio were evaluated. Results: The presence of neutrophils and the neutrophil-to-lymphocyte ratio correlated with high-grade urothelial neoplasms. In both low- and high-grade tumors, the lymphocytes increased during progression from a non-invasive neoplasm to an early-invasive neoplasm. CD8+ T lymphocytes increased in low-grade non–muscle-invasive tumors compared to non-invasive tumors. Additionally, there was a significant decrease in CD8+ T lymphocytes during progression to muscle-invasive tumors. Conclusions: Our results suggest that tumor-infiltrating neutrophils and CD8+ T lymphocytes have a significant effect on tumor grade and progression.
Abstract
Background: Tumor-infiltrating neutrophils and lymphocytes play essential roles in promoting or combating various neoplasms. This study aimed to investigate the association between tumor-infiltrating neutrophils and lymphocytes and the neutrophil-to-lymphocyte ratio in the progression of urothelial carcinoma. Methods: A total of 106 patients diagnosed with urothelial carcinoma were was. Pathological examination for tumor grade and stage and for tumor-infiltrating neutrophils, both CD4 and CD8+ T lymphocytes, as well as the neutrophil- to-lymphocyte ratio were evaluated. Results: The presence of neutrophils and the neutrophil-to-lymphocyte ratio correlated with high-grade urothelial neoplasms. In both low- and high-grade tumors, the lymphocytes increased during progression from a non-invasive neoplasm to an early-invasive neoplasm. CD8+ T lymphocytes increased in low-grade non–muscle-invasive tumors compared to non-invasive tumors. Additionally, there was a significant decrease in CD8+ T lymphocytes during progression to muscle-invasive tumors. Conclusions: Our results suggest that tumor-infiltrating neutrophils and CD8+ T lymphocytes have a significant effect on tumor grade and progression.
참고문헌 (42)
- Bray F, "Global cancer statistics 2018 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries", CA Cancer J Clin, 68, pp.394~424 (2018)
- Miyazaki J, "Epidemiology of urothelial carcinoma", Int J Urol, 24, pp.730~734 (2017)
- Kamat AM, "Bladder cancer", Lancet, 388, pp.2796~2810 (2016)
- Chang SS, "Diagnosis and treatment of non-muscle invasive bladder cancer : AUA", SUO guideline, 2016, pp.196, 1021~1029
- Mathieu R, "Trimodal therapy for invasive bladder cancer : is it really equal to radical cystectomy?", Curr Opin Urol, 25, pp.476~482 (2015)
- Ceylan C, "Importance of the neutrophil-to-lymphocyte ratio in muscle-invasive and non-muscle invasive bladder tumors", Urologia, 81, pp.120~124 (2014)
- Abdou Hassan W, "Evaluation of the expression of HER2 and c-KIT proteins as prognostic markers in superficial bladder urothelial carcinoma", Res Rep Urol, 13, pp.197~206 (2021)
- Lobo N, "Landmarks in the treatment of muscle-invasive bladder cancer", Nat Rev Urol, 14, pp.565~574 (2017)
- Gakis G, "The prognostic value of hematological and systemic inflammatory disorders in invasive bladder cancer", Curr Opin Urol, 21, pp.428~433 (2011)
- Schepisi G, "Urothelial cancer : inflammatory mediators and implications for immunotherapy", BioDrugs, 30, pp.263~273 (2016)
- Cavallo F, "2011 : the immune hallmarks of cancer", Cancer Immunol Immunother, 60, pp.319~326 (2011)
- Amulic B, "Neutrophil function : from mechanisms to disease", Annu Rev Immunol, 30, pp.459~489 (2012)
- Mano R, "Neutrophil-to-lymphocyte ratio predicts progression and recurrence of non-muscle-invasive bladder cancer", Urol Oncol, 33, pp.67~ (2015)
- Gondo T, "Prognostic value of neutrophil-to-lymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy", Urology, 79, pp.1085~1091 (2012)
- Ho WY, "Adoptive therapy with CD8(+)T cells : it may get by with a little help from its friends", J Clin Invest, 110, pp.1415~1417 (2002)
- Sato E, "Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+", regulatory T cell ratio are associated with favorable prognosis in ovarian cancer, 2005, pp.102, 18538~18543
- Sheu BC, "Reversed CD4", CD8 ratios of tumor-infiltrating lymphocytes are correlated with the progression of human cervical carcinoma, 1999, pp.86, 1537~1543
- Sharma MD, "Indoleamine 2, 3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes", Blood, 113, pp.6102~6111 (2009)
- Comperat EM, "Grading of urothelial carcinoma and the new"World Health Organisation classification of tumours of the urinary system and male genital organs 2016"", Eur Urol Focus, 5, pp.457~466 (2019)
- Uribe-Querol E, "Neutrophils in cancer : two sides of the same coin", J Immunol Res, 2015, pp.983698~ (2015)
- Liu K, "The prognostic values of tumor-infiltrating neutrophils, lymphocytes and neutrophil", lymphocyte rates in bladder urothelial cancer, 2018, pp.214, 1074~1080
- Jensen HK, "Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma", J Clin Oncol, 27, pp.4709~4717 (2009)
- Trellakis S, "Polymorphonuclear granulocytes in human head and neck cancer : enhanced inflammatory activity, modulation by cancer cells and expansion in advanced disease", Int J Cancer, 129, pp.2183~2193 (2011)
- Naso JR, "Tumor infiltrating neutrophils and gland formation predict overall survival and molecular subgroups in pancreatic ductal adenocarcinoma", Cancer Med, 10, pp.1155~1165 (2021)
- Lin C, "Infiltrating neutrophils increase bladder cancer cell invasion via modulation of androgen receptor(AR)", MMP13 signals, 2015, pp.6, 43081~43089
- Joseph M, "Immune responses in bladder cancer-role of immune cell populations, prognostic factors and therapeutic implications", Front Oncol, 9, pp.1270~ (2019)
- Schreiber RD, "Cancer immunoediting : integrating immunity’s roles in cancer suppression and promotion", Science, 331, pp.1565~1570 (2011)
- Kim HS, "Prognostic impact of tumor infiltrating lymphocytes in bladder urothelial carcinoma", Transl Androl Urol, 8(Suppl 3), pp.S291~S292 (2019)
- Rouanne M, "Stromal lymphocyte infiltration is associated with tumour invasion depth but is not prognostic in high-grade T1 bladder cancer", Eur J Cancer, 108, pp.111~119 (2019)
- Pichler R, "Tumorinfiltrating immune cell subpopulations influence the oncologic outcome after intravesical bacillus Calmette-Guerin therapy in bladder cancer", Oncotarget, 7, pp.39916~39930 (2016)
- Masson-Lecomte A, "CD8+ cytotoxic immune infiltrate in non-muscle invasive bladder cancer : a standardized methodology to study association with clinico-pathological features and prognosis", Bladder Cancer, 5, pp.159~169 (2019)
- Li F, "The association between CD8+ tumor-infiltrating lymphocytes and the clinical outcome of cancer immunotherapy : a systematic review and meta-analysis", EClinicalMedicine, 41, pp.101134~ (2021)
- Faraj SF, "Assessment of tumoral PD-L1expression and intratumoral CD8+ T cells in urothelial carcinoma", Urology, 85, pp.703~ (2015)
- Hulsen S, "High stroma T-cell infiltration is associated with better survival in stage pT1 bladder cancer", Int J Mol Sci, 21, pp.8407~ (2020)
- Zhang Q, "High CD4(+) T cell density is associated with poor prognosis in patients with non-muscle-invasive bladder cancer", Int J Clin Exp Pathol, 8, pp.11510~11516 (2015)
- Yu A, "Presence of lymphocytic infiltrate cytotoxic T lymphocyte CD3+, CD8+, and immunoscore as prognostic marker in patients after radical cystectomy", PLoS One, 13, pp.e0205746~ (2018)
- Shi MJ, "High CD3D", CD4 ratio predicts better survival in muscle-invasive bladder cancer, 2019, pp.11, 2987~2995
- Favilla V, "Neutrophil to lymphocyte ratio, a biomarker in non-muscle invasive bladder cancer : a single-institutional longitudinal study", Int Braz J Urol, 42, pp.685~693 (2016)
- Kawahara T, "Neutrophil-to-lymphocyte ratio is a prognostic marker in bladder cancer patients after radical cystectomy", BMC Cancer, 16, pp.185~ (2016)
- Tazeh NN, "Neutrophil to lymphocyte ratio(NLR)at the time of transurethral eesection of bladder tumor : a large retrospective study and analysis of racial differences", Bladder Cancer, 3, pp.89~94 (2017)
- Mandelli GE, "Tumor infiltrating neutrophils are enriched in basal-type urothelial bladder cancer", Cells, 9, pp.291~ (2020)
- Nukui A, "Association of cancer progression with elevated expression of programmed cell death protein 1 ligand 1 by upper tract urothelial carcinoma and increased tumor-infiltrating lymphocyte density", Cancer Immunol Immunother, 69, pp.689~702 (2020)
