Phenotypic Analysis of Tumor Tissue-Infiltrating Lymphocytes in Tumor Microenvironment of Bladder Cancer and Upper Urinary Tract Carcinoma

Clin Genitourin Cancer. 2019 Apr;17(2):114-124. doi: 10.1016/j.clgc.2018.11.004. Epub 2018 Nov 17.

Abstract

Background: There are no previous reports directly evaluating immunologic conditions in tumor microenvironment including both bladder cancer (BCa) and upper urinary tract carcinoma (UTUC). In this study, we aimed to clarify the difference of immunity status and its clinical significance depending on the tumor site in urothelial carcinoma.

Patients and methods: Tumor tissue-infiltrating lymphocytes were extracted from 70 urothelial cancer patients who underwent surgical resection (52 cases of BCa and 18 cases of UTUC). The immunologic classification was established by unsupervised clustering analysis according to the expression ratio of 9 extracellular surface markers measured by flow cytometry, and we examined the relationship between immunologic classification and clinical importance such as pathologic status and prognosis (progression-free survival and cancer-specific survival).

Results: The immunologic condition was classified into 2 groups. Group 1 (n = 41) comprised the CD4 T-cell-dominant group and group 2 (n = 29) the immunologically activated group. This immunologic classification was significantly correlated with tumor grade (P = .020) but not tumor location in multivariate analysis. In invasive BCa patients (n = 33), progression-free survival and cancer-specific survival of group 2 were significantly worse than those of group 1 (P = .021 and P = .022, respectively), while there was no significant difference between groups 1 and 2 in patients with invasive UTUC (n = 17).

Conclusion: Although there was no difference in the local immunologic condition of urothelial carcinoma between BCa and UTUC, its significance as a prognostic predictor might vary depending on tumor site.

Keywords: Heterogeneity; Immune checkpoint; Prognosis; Tumor tissue-infiltrating lymphocytes; Urothelial carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • CD4-Positive T-Lymphocytes / metabolism*
  • Carcinoma, Transitional Cell / immunology
  • Carcinoma, Transitional Cell / pathology*
  • Carcinoma, Transitional Cell / surgery
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Prognosis
  • Survival Analysis
  • Tumor Microenvironment
  • Urinary Bladder Neoplasms / immunology
  • Urinary Bladder Neoplasms / pathology*
  • Urinary Bladder Neoplasms / surgery

Substances

  • Biomarkers, Tumor