Tumor Microenvironment Mediators CD8+- and FOXP3+-Labeled T Lymphocytes Are Prospective Prognosticators in Curatively Treated Rectal Cancer Patients

J Gastrointest Cancer. 2021 Mar;52(1):177-186. doi: 10.1007/s12029-020-00376-1.

Abstract

Purpose: To explore the implication of CD8+- and FOXP3+-labeled T lymphocytes invading tumor microenvironment in prognosticating curatively treated rectal cancer with preoperative chemo-radiation.

Methods: The diagnostic rectal biopsies from clinical T3-T4 and any nodal diseases or any T stage with nodal involvement were processed to quantify (CD8+and FOXP3+). The impact of tested indicators on the achieved pathologic response among other clinical-pathological variables was particularized. Additionally, the prognosticating eventuality of labeled T lymphocytes for survival was elaborated using Log-rank and Cox regression.

Results: We selected fifty rectal patients who had negative surgical margins following preoperative chemo-radiation for clinical T3-T4 or any T stage with nodal involvement. The higher expressions of CD8+ and CD8+/FOXP3+, and the reduced FOXP3+incursion were interrelated with the lack of nodal and lympho-vascular invasion alongside accentuated pathologic response. Additionally, the augmented densities of FOXP3+ ≥ 120, the reduced CD8+/FOXP3+ ratio < 0.96, and the nodal incursion were considerably linked with the worsened OS [hazard ratio (HR) 2.37 (95% confidence interval (CI), 2.38-11.27), 2.41 (95% CI, 2.14-7.12), and 2.63 (95% CI, 2.81-5.32)], and dismal DFS [HR 2.61 (95% CI, 1.58-6.12), 3.12 (95% CI, 2.15-7.24), and 3.32 (95% CI, 2.47-9.24)], respectively.

Conclusion: The augmented expressions of CD8+ and C8+/FOXP3+ together with the reduced densities of FOXP3+ exhibited a substantial contribution to the attained pathological response and were linked to improved clinical-pathological characteristics of cancer rectum patients treated with chemo-radiation preceding mesorectal excision. Additionally, they can be authorized as reliable individual prognosticators of clinical outcomes.

Keywords: CD8+; Cancer; FOXP3+; Prognosticators; Rectal; T Lymphocytes.

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Chemoradiotherapy / methods
  • Disease-Free Survival
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / prevention & control
  • Neoplasm Staging
  • Proctectomy
  • Prognosis
  • Prospective Studies
  • Rectal Neoplasms / diagnosis
  • Rectal Neoplasms / immunology
  • Rectal Neoplasms / mortality*
  • Rectal Neoplasms / therapy
  • Rectum / immunology
  • Rectum / pathology
  • Rectum / surgery
  • Tumor Microenvironment / immunology*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors