CD8+ lymphocyte intratumoral infiltration as a stage-independent predictor of Merkel cell carcinoma survival: a population-based study

Abstract

Objectives: Intratumoral CD8+ lymphocytes (IT-CD8s) have shown promise as a prognostic indicator for Merkel cell carcinoma (MCC). We tested whether IT-CD8s predict survival among a population-based MCC cohort.

Methods: One hundred thirty-seven MCC cases that had not previously been analyzed for IT-CD8s were studied.

Results: Three-year MCC-specific survival rates were 56%, 72%, and 100% for patients with absent (n = 46), low (n = 85), and moderate or strong (n = 6) IT-CD8s, respectively. Increased IT-CD8s were associated with improved MCC-specific survival in a multivariate competing risk-regression analysis including stage, age, and sex (hazard ratio [HR] = 0.5; 95% confidence interval [CI] = 0.3-0.9). Although a similar trend was observed for overall survival, statistical significance was not reached (HR = 0.8; 95% CI = 0.6-1.0), likely because of the high rate of non-MCC deaths among older patients.

Conclusions: This study of prospectively captured MCC cases supports the concept that cellular immunity is important in MCC outcome and that CD8+ lymphocyte infiltration adds prognostic information to conventional staging.

Keywords: Merkel cell carcinoma; Survival; T cells.

Figure 1

CD8+ lymphocyte infiltration and Merkel cell carcinoma (MCC) survival. A, MCC-specific survival rates using Kaplan-Meier curves for patients with absent, low, and moderate-strong intratumoral CD8+ infiltration, respectively, were 77%, 91%, 100% at 1 year; 56%, 72%, 100% at 3 years; and 45%, 64%, 100% at 5 years. B, Overall survival rates for patients with absent, low, and moderate-strong intratumoral CD8+ infiltration, respectively, were 63%, 84%, 83% at 1 year; 39%, 49%, 83% at 3 years; and 22%, 34%, 67% at 5 years. Data are shown for purposes of visualization. (See Tables 2 and 3 for univariate and multivariate Cox regression statistical analysis.)

Image 1

Merkel cell tumor (MCC) tumor scores for intratumoral (IT) CD8+ cells. A, H&E staining of MCC tumor. B, Anti-CD8 staining of the same tumor demonstrating peritumoral and IT-CD8+ cells: IT-CD8+ cells must be surrounded by tumor cells and not have direct contact with stroma. MCC tumors showing varying scores of IT-CD8+ cell infiltration per high-power field (hpf) scored semiquantitatively as follows: score 0: 0 cells/mm² per hpf (C), score 1: approximately 1-179 cells/mm² per hpf (D), score 2: approximately 180-433 cells/mm² per hpf. (E), score 3: approximately 434-582 cells/mm² per hpf (F), score 4: approximately 583-731 cells/mm² per hpf (G) and score 5: ≥732 cells/mm2 per hpf (H).

Image 1

Merkel cell tumor (MCC) tumor scores for intratumoral (IT) CD8+ cells. A, H&E staining of MCC tumor. B, Anti-CD8 staining of the same tumor demonstrating peritumoral and IT-CD8+ cells: IT-CD8+ cells must be surrounded by tumor cells and not have direct contact with stroma. MCC tumors showing varying scores of IT-CD8+ cell infiltration per high-power field (hpf) scored semiquantitatively as follows: score 0: 0 cells/mm² per hpf (C), score 1: approximately 1-179 cells/mm² per hpf (D), score 2: approximately 180-433 cells/mm² per hpf. (E), score 3: approximately 434-582 cells/mm² per hpf (F), score 4: approximately 583-731 cells/mm² per hpf (G) and score 5: ≥732 cells/mm2 per hpf (H).