Characterization of the tumor immune microenvironment in human papillomavirus-positive and -negative head and neck squam
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ORIGINAL ARTICLE
Characterization of the tumor immune microenvironment in human papillomavirus‑positive and ‑negative head and neck squamous cell carcinomas Farah Succaria1 · Pia Kvistborg2 · Julie E. Stein1 · Elizabeth L. Engle3,4 · Tracee L. McMiller4,5 · Lisa M. Rooper6 · Elizabeth Thompson4,6 · Alan E. Berger5 · Michiel van den Brekel2 · Charlotte L. Zuur2 · John Haanen2 · Suzanne L. Topalian4,5 · Janis M. Taube1,3,4 Received: 18 February 2020 / Accepted: 12 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Approximately 15% of advanced head and neck squamous cell carcinomas (HNSCC) respond to anti-PD-(L)1 monotherapies. Tumor PD-L1 expression and human papillomavirus (HPV) status have been proposed as biomarkers to identify patients likely to benefit from these treatments. We aimed to understand the potential immune effects of HPV in HNSCC and to characterize additional potentially targetable immune-regulatory pathways in primary, treatment-naïve tumors. CD3, CD4, CD8, CD20, CD68, FoxP3, PD-1, PD-L2, LAG-3, IDO-1, and GITR cell densities were determined in 27 HNSCC specimens. IHC for PD-L1 assessed percentage of positive tumor cells and immune cells separately or as a combined positive score (CPS), and whether PD-L1 was expressed in an adaptive or constitutive pattern (i.e., PD-L1+ tumor cells juxtaposed to TILs or in the absence of TILs, respectively). HPV testing with p16 IHC was confirmed by HPV genotyping. When compared to HPV(−) tumors (n = 14), HPV+ tumors (n = 13) contained significantly higher densities of CD3+, CD4+, CD8+, CD20+, and PD-1+ cells (P 500 IDO-1+ cells/mm2 in 17/27 specimens) and was found on tumor cells as well as immune cells in 12/27 (44%) cases (range 5–80% tumor cells+). Notably, the studied markers varied on a per-patient basis and were not always related to the degree of T cell infiltration. These findings may inform therapeutic co-targeting strategies and raise consideration for a personalized treatment approach. Keywords Head and neck squamous cell carcinoma (HNSCC) · PD-1 · PD-L1 · HPV · IDO · GITR
Introduction
Farah Succaria and Pia Kvistborg have contributed equally to this work. Suzanne L. Topalian and Janis M. Taube have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00262-020-02747-w) contains supplementary material, which is available to authorized users. * Janis M. Taube [email protected] Extended author information available on the last page of the article
Head and neck squamous cell carcinoma (HNSCC) is a major cause of cancer morbidity and mortality worldwide [1]. It includes human papillomavirus-positive (HPV+) and -negative HPV(−) subtypes. In the United States, the incidence of HPV-associated HNSCC is on the rise [2]. Even with the use of multi-modality treatment regimens including surgery, chemotherapy, radiotherapy, and targeted therapy, approximately half of treated patients experience disease recurrence or progression [3]. Therapies block
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