The prognostic impact of the immune microenvironment in small-cell neuroendocrine carcinoma of the uterine cervix: PD-L1 and immune cell subtypes

Xiaoying Sun; Lili Liu; Ting Wan; Qidan Huang; Jieping Chen; Rongzhen Luo; Jihong Liu

doi:10.1186/s12935-022-02716-6

The prognostic impact of the immune microenvironment in small-cell neuroendocrine carcinoma of the uterine cervix: PD-L1 and immune cell subtypes

Cancer Cell Int. 2022 Nov 14;22(1):348. doi: 10.1186/s12935-022-02716-6.

Authors

Xiaoying Sun^#^{1

2}, Lili Liu^#¹, Ting Wan¹, Qidan Huang¹, Jieping Chen¹, Rongzhen Luo^{3

4}, Jihong Liu^{5

6}

Affiliations

¹ State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, Guangzhou, 510060, China.
² Department of Gynecology, Guangdong Provincial People's Hospital, Guangzhou, People's Republic of China, 510080, Guangdong.
³ State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, Guangzhou, 510060, China. luorzh@sysucc.org.cn.
⁴ State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Pathology, Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, Guangzhou, 510060, China. luorzh@sysucc.org.cn.
⁵ State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, Guangzhou, 510060, China. liujih@mail.sysu.edu.cn.
⁶ State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Department of Gynecologic Oncology, Cancer Center, Sun Yat-Sen University, No. 651, Dongfeng Road East, Guangzhou, 510060, China. liujih@mail.sysu.edu.cn.

^# Contributed equally.

Abstract

Background: We investigate the correlation between programmed cell death-ligand 1 (PD-L1) and tumor-associated immune cell (TAIC) density in small-cell neuroendocrine carcinoma of the uterine cervix (SCNEC) and their correlation with clinicopathologic features.

Methods: PD-L1 and mismatch repair protein (MMR) expression in cancer cells and the density of TAIC were evaluated by immunohistochemistry in 89 SCNEC patients. The combined positive score (CPS), tumor proportion score (TPS), and immune cell score (ICS) of PD-L1 were measured, along with their correlation with clinicopathologic features in SCNEC patients using statistical analyses.

Results: CPS of PD-L1 ≥ 1 was seen in 68.5% of patients, positive TPS and ICS of PD-L1 were detected in 59.6% and 33.7% of patients, respectively. PD-L1^CPS was higher in tumor-infiltrating immune cells (r = 0.387, p = 0.001) and positively correlated with programmed cell death-1 and forkhead box P3 + regulatory T cell (FOXP3 + Treg) infiltration (r = 0.443, p < 0.001; r = 0.532, p < 0.001). There was no statistical correlation between PD-L1 and MMR status. PD-L1^CPS and PD-L1^ICS positivity were independent prognostic factors, correlating with a favorable survival (HR (95%CI) = 0.363(0.139-0.950), p = 0.039 and HR (95% CI) = 0.199(0.050-0.802), p = 0.023, respectively). PD-L1^ICS positivity was an independent indicator of recurrence in SCNEC patients and associated with better disease-free survival (HR (95% CI) = 0.124(0.036-0425), p = 0.001). TAIC and MMR levels had no statistical impact on survival results.

Conclusions: PD-L1 positivity was seen in over half of SCNEC tumors. It may work synergistically with FOXP3 + Treg and other infiltrating immune cells to support an adaptive immune response. PD-L1 positivity may be a favorable prognostic factor in SCNEC.

Keywords: FOXP3; PD-L1; Small-cell neuroendocrine carcinoma of the cervix; TILs.