PD-L1 Expression in Endocervical Adenocarcinoma

Abstract

Programmed death-1 ligand (PD-L1) expression has been used as a predictive marker for response to immune checkpoint inhibitors and has been reported to have prognostic value. Its prevalence and significance in endocervical adenocarcinoma (ECA) remain underinvestigated. We evaluated PD-L1 expression and CD8+ tumor-infiltrating lymphocyte density in whole tissue sections of 89 ECAs. PD-L1 expression was observed in 68% of ECAs by combined positive score (CPS, cutoff 1) and 29% of ECAs by tumor proportion score (TPS, cutoff 1%). Using CPS, PD-L1 expression was seen in 11%, 78%, and 72% of pattern A, B, and C tumors, respectively, with significantly higher expression in tumors with destructive-type invasion (B and C) (P=0.001 [A vs. B], 0.0006 [A vs. C], 0.0002 [A vs. B+C]). Using TPS, no significant difference in PD-L1 expression was seen between tumors with different invasion patterns (0%, 22%, and 32% in tumors with pattern A, B, and C, respectively; P=0.27 [A vs. B], 0.053 [A vs. C], 0.11 [A vs. B+C]). PD-L1-positive ECAs demonstrated significantly higher CD8+ tumor-infiltrating lymphocyte density (CPS: P=0.028; TPS: P=0.013) and worse progression-free survival when compared with PD-L1-negative ECAs (CPS: hazard ratio [HR]=4.253 vs. 0.235, P=0.025; TPS: HR=4.98 vs. 0.2; P=0.004). When invasion patterns were separately assessed, pattern C tumors similarly showed worse progression-free survival in PD-L1-positive tumors (CPS: HR=6.15 vs. 0.16, P=0.045; TPS: HR=3.78 vs. 0.26, P=0.027). In conclusion, our data show frequent PD-L1 expression in ECA with destructive-type invasion, supporting the role of the PD-1/PD-L1 pathway as a therapeutic target for these tumors. Our data also support PD-L1 as a negative prognostic marker associated with a potentially unfavorable outcome.

The Prognostic Values of HPV Genotypes and Tumor PD-L1 Expression in Patients With HPV-associated Endocervical Adenocarcinoma

“…As one of the most important immune checkpoints, several studies have investigated PD-L1 prevalence in cervical cancers. 21,[55][56][57][58][59][60][61][62][63][64] Studies have demonstrated a significant correlation between HPV infection and increased PD-L1 expression in cervical SCC and cervical intraepithelial neoplasia. 60,61,63,65 Although the underlying mechanism is not fully understood, those studies suggested impaired immune surveillance by the upregulated PD-L1 expression caused by HPV infection plays a crucial role in the SCC/cervical intraepithelial neoplasia development.…”

“…Most recently, a study by Rivera-Colon et al 21 suggested that PD-L1 may be an unfavorable prognostic marker for ECAs. Similar to that study, our data demonstrated a high prevalence of PD-L1 in usual-type HPVA ECAs (25% by TPS and 55% by CPS).…”

“…19,20 Most recently, PD-L1 expression has been shown to be a negative prognostic marker associated with a potentially unfavorable outcome for ECAs. 21 Despite the well-established pathogenic effect of highrisk human papillomavirus (hrHPV) genotypes for ECAs, 22 the prognostic values of hrHPV genotypes in patients with HPVA ECAs have not been established. HPV genotypes 16,18, and 45 accounted for ∼95% of HPVA ECA.…”

CMTM6 recruits T cells within the endocervical adenocarcinoma microenvironment and suppresses cell proliferation via the p53 pathway

“…Notably, heterogenous intratumoral PD‐L1 expression is frequently observed in ECA, which could impact the effectiveness of PD‐L1‐directed immunotherapy in these cancers. Moreover, PD‐L1 expression in ECA patterns B and C was significantly increased compared to other patterns 13 . It was also found that gastric adenocarcinoma (GEA) tumors expressing PD‐L1 have worse outcomes than GEA tumors that do not expression PD‐L1 14 .…”

“…Moreover, PD-L1 expression in ECA patterns B and C was significantly increased compared to other patterns. 13 It was also found that gastric adenocarcinoma (GEA) tumors expressing PD-L1 have worse outcomes than GEA tumors that do not expression PD-L1. 14 In addition, TILs play an important role in the development of cervical cancer.…”