Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma
By Sofia Lyford-Pike, S. Peng, Geoffrey D. Young, Janis Taube, W. Westra, B. Akpeng, T. Bruno, J. Richmon, Hao Wang, J. Bishop and 5 more. Cancer Research, 2013
738 citations recorded by the source corpus.
Human papillomavirus-associated head and neck squamous cell carcinomas (HPV-HNSCC) originate in the tonsils, the major lymphoid organ that orchestrates immunity to oral infections. Despite its location, the virus escapes immune elimination during malignant transformation and progression. Here, we provide evidence for the role of the PD-1:PD-L1 pathway in HPV-HNSCC immune resistance. We demonstrate membranous expression of PD-L1 in the tonsillar crypts, the site of initial HPV infection. In HPV-HNSCCs that are highly infiltrated with lymphocytes, PD-L1 expression on both tumor cells and CD68+ tumor associated macrophages (TAMs) is geographically localized to sites of lymphocyte fronts, while the majority of CD8+ tumor infiltrating lymphocytes (TILs) express high levels of PD-1, the inhibitory PD-L1 receptor. Significant levels of mRNA for interferon-γ (IFN-γ), a major cytokine inducer of PD-L1 expression, were found in HPV+ PD-L1(+) tumors. Our findings support the role of the PD-1:PD-L1 interaction in creating an “immune-privileged” site for initial viral infection and subsequent adaptive immune resistance once tumors are established and suggest a rationale for therapeutic blockade of this pathway in patients with HPV-HNSCC.
Subfields: Cancer Research, Oncology, Otorhinolaryngology
View Paper: https://www.semanticscholar.org/paper/8b0b003d77baf05221c4788a91320decc683a12a
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Citations in the corpus
- Immunology and Immunotherapy of Head and Neck Cancer. (2015, background): “During normal immune responses, the presence of checkpoint receptors, such as PD-1 or CTLA-4, limits an overrobust immune response to protect from autoimmune reactivity.(62,63) In patients with HNSCC, elevated PD-1 expression has been observed on CD8 HPVpositive tumor-infiltrating lymphocytes(64) bu”
- Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort (2016, background): “of previous lines of therapy for recurrent or metastatic disease 0 24 (18) 1 33 (25) 2 27 (21) 3 20 (15) 4 15 (11) $ 5 13 (10)”