The roles of cd8+ ctls, cd163+ tams, pdl1 in tumor microenvironment in the prognosis of primary central nervous system

Introduction: In order to explore the immune cell infiltration and PDL1 expression in the tumor microenvironment (TME) of primary central nervous system lymphoma (PCNSL), we conducted this research and discussed the therapeutic importance and prognostic significance of TME. Methods: Immunohistochemical staining was performed on paraffin-embedded tumor tissues of 36 patients diagnosed with PCNSL. 3–5 fields were taken to represent the whole TME. CD8 and CD163 positive cells were manually counted (numbers/HPF). PDL1 was quantified by H-Score scoring method in the tumor center and around the tumor (within 3 cm outside the tumor area) respectively. The Kaplan-Meier method was used to reveal the prognostic significance of TME. Results: We found obvious infiltration of CD8+ CTLs and CD163+ TAMs in the TME of PCNSL, and the average number of CD8+ CTLs was 59/HP and CD163+ TAMs was 38 /HP. The CD8+ CTLs is more than CD163+ TAMs (p = 0.012). Meanwhile, PDL1 was expressed in tumor center as well as around the tumor. The average PDL1 H-Score in the tumor center was 20.98, and which around the tumor was 37.38. The expression of PDL1 around the tumor was significantly higher than that in the tumor center (p < 0.0001). It is notable that the expression of PDL1, both in the tumor center and around the tumor, was significantly correlated with CD163+ TAMs (PDL1 in the tumor center: r = 0.42, p = 0.015, PDL1 around the tumor: r = 0.40, p = 0.021). The cut-off values of CD8+ CTLs, CD163+ TAMs and PDL1 were obtained by ROC curve, then the survival analysis showed that high CD8+ CTLs (p = 0.027) and high PDL1 expression in the tumor center (p = 0.012) were significantly correlated with longer overall survival (OS). High CD8+ CTLs (p = 0.044) and high CD163+ TAMs (p = 0.040) were associated with longer progression-free survival (PFS). There was no significant correlation between PDL1 around the tumor and prognosis. Furthermore, the patients were divided into ORR group and non-ORR group according to whether they achieved objective response to treatment or not. We found that CD163+ TAMs was increased in ORR group (p = 0.012). Finally, the χ2 test showed that the CD163+ TAMs was related to age (p = 0.042), and the expression of PDL1 around the tumor was related to serum LDH level (p = 0.002). The research was funded by: the National Natural Science Foundation of China [grant number 8226010026] and the “Cui Ying graduate instructor” training program of Lanzhou University Second Hospital [grant number 201710]. Keywords: aggressive B-cell non-Hodgkin lymphoma, diagnostic and prognostic biomarkers, extranodal non-Hodgkin lymphoma No conflicts of interests pertinent to the abstract.