Immune cell densities, HLA status, and PD-L1 expression in stage I neuroendocrine neoplasm of the uterine cervix

Abstract

Neuroendocrine neoplasms (NENs) of the uterine cervix are highly malignant tumors associated with a poor prognosis. Human papillomavirus test-based uterine cervical cancer screening methods can detect early-stage uterine cervical NENs, so therapeutic strategies for the earliest stages are urgently needed. This study aimed to investigate and evaluate the prognostic significance of intratumoral and stromal immune cell densities, as well as human leukocyte antigen (HLA) and programmed cell death ligand 1 (PD-L1) expression in stage I uterine cervical NENs. Sixteen NENs were identified, including 8 large cell neuroendocrine carcinomas (LCNECs), 4 small cell neuroendocrine carcinomas (SCNECs), 3 neuroendocrine tumors (NETs), and 1 LCNEC with an SCNEC component. Only 3 cases were pure NENs, while 13 cases included a component of adenocarcinoma or squamous cell carcinoma. Eight of the 16 patients experienced postoperative recurrence. The recurrence-free group exhibited significantly higher densities of intratumoral CD3- and CD8-positive cells compared to the recurrence group (median densities: 136 vs. 48 cells/mm², P = 0.0281 and 91 vs. 27 cells/mm², P = 0.0359, respectively). No significant differences in clinicopathological characteristics, other immune cell densities, or expression of HLA class I, HLA-DR, or PD-L1 were observed between groups. HLA-DR expression was nearly absent in uterine cervical NENs, whereas adjacent non-NEN components displayed varying degrees of HLA-DR expression. PD-L1 expression was observed in 25 % of cases, with CD3- and CD8-positive T-cell-rich stroma. The observed modifications to tumor microenvironments could offer clues to future treatments for uterine cervical NEN. (240/250 words)