Clinical Relevance of PD-L1 Expression and CD8+ T Cells' Infiltration in Patients With Lung Invasive Mucinous Adenocarcinoma

Xiaoling Xu; Na Li; Ding Wang; Wei Chen; Yun Fan

doi:10.3389/fonc.2021.683432

Clinical Relevance of PD-L1 Expression and CD8+ T Cells' Infiltration in Patients With Lung Invasive Mucinous Adenocarcinoma

Front Oncol. 2021 Jun 24:11:683432. doi: 10.3389/fonc.2021.683432. eCollection 2021.

Authors

Xiaoling Xu^{1

2

3}, Na Li^{2

3}, Ding Wang³, Wei Chen², Yun Fan^{1

2

3}

Affiliations

¹ Key Laboratory of Head & Neck Cancer Translational Research of Zhejiang Province, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.
² Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, China.
³ Department of Medical Oncology, The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, China.

Abstract

Background: Invasive mucinous adenocarcinoma (IMA) of the lung is a rare and distinct subtype of adenocarcinoma. At present, people have no idea whether IMA patients can benefit from immunotherapy and target therapy; thus there is an urgent need to clarify the immune microenvironment and genetic characteristics of this cohort.

Methods: A total of 31 IMA patients matched with 27 non-mucinous adenocarcinoma (non-IMA) patients were enrolled in this study, and clinical data was collected. The expression of PD-L1, CD8+ tumor-infiltrating lymphocytes (TILs) and ALK was determined by immunohistochemistry. Polymerase Chain Reaction was used to determine the mutations of EGFR. The Chi-square test, Kaplan-Meier method and Cox proportional hazard regression model were used to explore the correlations between these clinicopathological variables, survival and identify risk factors.

Results: Of the patients with IMA 9.7% (3/31) revealed positive PD-L1 expression and 35.5% (11/31) showed CD8+ TIL infiltration, which were markedly lower than that of non-IMA group [PD-L1: 48.1% (13/27); CD8: 81.5% (22/27)]. Moreover, five (16.1%) patients in IMA group and 10 (37.0%) patients in non-IMA group had EGFR mutations, and nine (29.0%) patients in IMA group and zero (0.0%) patient in non-IMA group had ALK rearrangements. Additionally, we observed that IMA patients with CD8+ TIL infiltration had a worse prognosis than CD8-negative group (P = 0.024). Multivariate analyses showed that CD8 was an independent prognostic factor for patient's survival (HR = 5.60, 95% CI: 1.35-23.22, P = 0.017).

Conclusion: Patients with IMA have down-regulated expression of PD-L1 and less CD8+ TIL infiltration in tumor microenvironment. Besides, a lower frequency of EGFR mutations was detected in patients with IMA than non-IMA patients while a higher rate of ALK rearrangements was found. Our results provide important reference for therapy of lung IMA.

Keywords: CD8+ T cells; PD-L1 expression; genetic characteristics; invasive mucinous adenocarcinoma; lung cancer; treatment; tumor microenvironment.