The Tumor-Specific Immune Landscape in HPV+ Head and Neck Cancer

Abstract

Human papillomaviruses (HPVs) are the causative agent of several anogenital cancers as well as head and neck cancers, with HPV+ head and neck squamous cell carcinoma (HNSCC) becoming a rapidly growing public health issue in the Western world. Due its viral etiology and potentially its subanatomical location, HPV+ HNSCC exhibits an immune microenvironment which is more inflamed and thus distinct from HPV-negative HNSCC. Notably, the antigenic landscape in most HPV+ HNSCC tumors extends beyond the classical HPV oncoproteins E6/7 and is extensively targeted by both the humoral and cellular arms of the adaptive immune system. Here, we provide a comprehensive overview of HPV-specific immune responses in patients with HPV+ HNSCC. We highlight the localization, antigen specificity, and differentiation states of humoral and cellular immune responses, and discuss their similarities and differences. Finally, we review currently pursued immunotherapeutic treatment modalities that attempt to harness HPV-specific immune responses for improving clinical outcomes in patients with HPV+ HNSCC.

IDO1 correlates with the immune landscape of head and neck squamous cell carcinoma: a study based on bioinformatics analyses

“…Interestingly, IDO1 is highly expressed especially in HPV+ HNSCC tumors compared with HPV− tumors. The high expression of IDO1 in HPV+ tumors can be explained in the context of high inflammation usually seen in this type of tumor in comparison with HPV− cases (25). We also conducted a comparison analysis of IDO1 expression levels in different cells between the primary tumor and metastatic lymph nodes.…”

Tumor Antigens beyond the Human Exome

“…Clinical trials with peptide-pulsed peripheral blood mononuclear cells (PBMCs) or DCs are conducted in patients with different HPV + cancers, but results are yet to be published (NCT00003977, NCT00019110, NCT00155766, and NCT03870113), as summarized in [169]. Adoptive cell therapies in HPV + HNSCC are used either via infusion of enriched HPV E6-and E7-specific TILs or via infusion of T cells expressing a T-cell receptor that recognizes HPV E6 or E7 peptides, as reviewed in [199]. Studies for both approaches have shown good clinical efficacy [200][201][202][203].…”

Tissue contexture determines the pattern and density of tumor-infiltrating immune cells in HPV-associated squamous cell carcinomas of oropharynx and uterine cervix

“…HPV-associated malignant tumors are caused by high-risk HPV subtypes, with HPV16 being detectable in more than 80 % of oropharyngeal squamous cell carcinomas and in 50–70 % of cervical cancers [1] , [2] , [3] . In general, HPV infects basal epithelial cells of the skin and mucosae.…”

“…There is evidence that early genes in addition to the classical oncoproteins E6 and E7 are expressed, such as E1, E2, and E5, when the HPV genome is episomally maintained [ 7 , 8 ]. The broader spectrum of the antigenic repertoire may thus lead to a stronger immune response in HPV-associated HNSCC than in cervical cancer [2] .…”