Stromal infiltrating CD8+ and CD20+ lymphocytes and CD204+ M2 macrophages but not PD-L1 expression on tumor cells are prognosticators for patients with resectable thymic carcinoma.

Abstract

e20002 Background: Thymic carcinoma (TMCA) is a rare malignant disease, and standard systemic chemotherapy has not been established. Tumor microenvironment (TME) that consists of tumor cells (TCs), tumor-infiltrating immune cells (TIICs) and stromal cells is thought to be an important biological feature of cancer behavior. The aim of this study was to analyze TME of TMCA, focusing the TIICs’ characteristics and the PD-L1 expression in the TC and TIIs and their impact on the clinical outcome. Methods: Fifty-one TMCA specimen with median observation period 33.8 months (range: 0.2-351) were collected. We evaluated the immunohistochemical profile of TIIs using antibodies against CD8, CD20 and FoxP3 for TIICs, CD204 for tumor-associated macrophages (TAMs), and PD-L1(SP142) expression of both TIICs and TCs using representative FFPE specimen. The density (median positive cell number per 1 mm2) of TIICs or TAMs was evaluated in intraepithelial (IE) and tumor stromal (TS) areas separately by using an automated image analyzer. Statistical analysis was performed using SPSS (version 24) and used p < 0.05 as significant level. Results: 51.9% (n = 26) had recurrent disease, and 31% (n = 16) survive without tumor. Of recurrent group, the density of CD8+ (54.5 vs 432) and CD20+ (35.9 vs. 516) TIIs, as well as the CD8+/CD204+, CD20+/CD204+ ratio in TS were significantly lower and FOXP3+ (590 vs 176) in TS was higher than that of non-recurrent group (Mann-Whitney U-test, two-sided). In the IE area, the lower CD20+/CD204+ ratio associated with recurrence. The CD20 and FOXP3 TIIs in TS also associated with the overall survival. There was no significant association between CD204 or PD-L1 expression and patients’ outcome. Conclusions: Our retrospective study showed the density of CD8+, CD20+ and FOXP3+ stromal-infiltrating lymphocytes and CD204+ M2 macrophage were prognostic factors for patients with resectable TMCA. Host immune reaction in TME might be one of the important prognostic factors for TMCA.