PD-L1 Expression and Immune Cell Infiltration in Gastroenteropancreatic (GEP) and Non-GEP Neuroendocrine Neoplasms With High Proliferative Activity

Frontiers in Oncology

Thomas J. Musholt¹  Matthias M. Weber²  Martina Ferrata²  Christian Fottner²  Katharina Bahr³  Julian Kuenzel³  Sven Becker³  Stefanie Zimmer⁴  Arno Schad⁴  Erik Springer⁴  Wilfried Roth⁴ 

[1] Clinic of General, Visceral- and Transplantation Surgery, Endocrine Surgery Section, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany;Department of Endocrinology and Metabolism, I Medical Clinic, University Hospital, Johannes Gutenberg University of Mainz, Mainz, Germany;Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany;Institute of Pathology, University Medical Center of the Johannes Gutenberg University of Mainz, Mainz, Germany;

关键词: neuroendocrine carcinoma;    immune checkpoint inhibitor;    PD-L1;    tumor associated immune cell;    neuroendocrine tumor;    neuroendocrine neoplasm;   

DOI  :  10.3389/fonc.2019.00343

来源: DOAJ

【 摘 要 】

The potential of neuroendocrine neoplasms (NEN) to respond to checkpoint inhibitors is largely unknown and full of great expectations. Immunohistochemical (IHC) studies of programmed cell death ligand 1 (PD-L1) expression in the tumor microenvironment and its implications in predicting the response to checkpoint inhibition is a very active subject. Currently, the combined analysis of PD-L1 expression and tumor-associated immune cell (TAIC) infiltration is considered the best predictive marker of therapeutic response. Here we investigated the expression of PD-L1 on tumor cells (TC) and tumor-infiltrating immune cells (IC) by IHC in 68 NEN samples with a high proliferation rate (Ki-67 >20%) from 57 patients and in 22 samples we correlated it with TAIC density by assessing intratumoral infiltration of CD3+, CD8+, and CD68+ cells. Furthermore, the tumor microenvironment was evaluated according to the classification of Teng et al. We detected PD-L1 expression in 31.6% of NEN G3. Its expression usually was weak and more IC than TC expressed PD-L1. The proportion of tumors positive for PD-L1 was comparable in NEN from different sites of origin but varied depending on tumor differentiation and disease extension. No positive IHC staining was found in 3 well-differentiated neuroendocrine tumors (NETs) with a proliferation rate above 20% (NET G3). When analyzing TAIC, we rarely (18.2%) detected intratumoral CD8+ cells, whereas infiltration by CD3+ and CD68+ cells was more common (45.5 and 59.1%, respectively). By combining CD3+ cells and PD-L1 status, we identified the immune ignorant phenotype of tumor microenvironment as being the most common phenotype, supporting the concept of a preferably combined immunotherapeutic approach in neuroendocrine carcinoma (NEC).

【 授权许可】

Unknown