Prognostic value of immunological profile based on CD8+ and FoxP3+ T lymphocytes in the peritumoral and intratumoral subsites for renal cell carcinoma

Int Urol Nephrol. 2020 Dec;52(12):2289-2299. doi: 10.1007/s11255-020-02592-x. Epub 2020 Aug 5.

Abstract

Purpose: We aimed to assess an "Immunological Profile (IP)" including CD8+ and FoxP3+ T lymphocytes for renal cell carcinoma (RCC) to evaluate its effects on tumor pathological characteristics, disease progression, and survival.

Methods: Adjacent normal and intratumoral specimens from 42 patients who had undergone radical nephrectomy for RCC were analyzed for counts of CD8+ and FoxP3+ T lymphocytes by immunohistochemistry. Tissue from both sites were evaluated and scored separately according to low (0) or high (1) expression of CD8 and FoxP3. A total score (min: 0, max: 4) was assigned to each patient. Thereafter, patients were divided into two groups for clinicopathologic and survival stratification based on score (IPWeak 0-2; and IPStrong 3-4). Survival curves were constructed using the Kaplan-Meier method, and a multivariable Cox regression model was used for overall survival (OS) and progression-free survival (PFS).

Results: The mean follow-up was 54.73 ± 21.34 months. Poor RCC characteristics including pT3-T4, tumor necrosis, lymphovascular invasion, lymph node involvement, and larger tumor size were significantly more common in the IPWeak patients compared to IPStrong (p < 0.05). Kaplan-Meier analysis showed that IPWeak patients had worse OS (62.5 vs. 100%; p = 0.006) and PFS (50 vs. 94.4%; p = 0.002) compared to IPStrong patients. In multivariable analysis, IPWeak (HR 8.64; 95% CI 1.09-68.05, p = 0.042) and high tumor node metastasis stage (HR 45.33; 95% CI 4.69-437.68, p < 0.001) were significant independent predictors of poor PFS.

Conclusion: Assessment of IP including CD8+ and FoxP3+ T lymphocytes in adjacent normal and intratumoral sites in RCC may serve as a good predictive marker for PFS.

Keywords: CD8; FoxP3; Immune scoring; Immunologic profile; RCC; Renal cell carcinoma.

MeSH terms

  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes*
  • Carcinoma, Renal Cell / immunology*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology*
  • Cohort Studies
  • Disease Progression
  • Female
  • Forkhead Transcription Factors / immunology*
  • Humans
  • Kidney Neoplasms / immunology*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology*
  • Male
  • Middle Aged
  • Prognosis
  • Survival Rate
  • T-Lymphocytes / immunology*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors