Current studies of immunotherapy in head and neck cancer

Doğan, Volkan; Rieckmann, Thorsten; Münscher, Adrian; Busch, Chia‐Jung

doi:10.1111/coa.12895

Cited by 60 publications

(46 citation statements)

References 31 publications

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“…A lack of tumor volume data for example, even though clearly linked to LRC (81,(84)(85)(86), impedes the assessment of a role for or a bias from tumor volumes in such analyses. To minimize such treatment or tumor site related bias due to possible interactions; we deliberately excluded the biologically distinct oral cavity and HPV-positive oropharyngeal HNSCC (14,16,(87)(88)(89)(90) in our study. Our cohort also solely comprises definitive chemo-radiotherapytreated advanced HNSCC.…”

Section: Discussionmentioning

confidence: 99%

Biological Determinants of Chemo-Radiotherapy Response in HPV-Negative Head and Neck Cancer: A Multicentric External Validation

et al. 2020

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Purpose: Tumor markers that are related to hypoxia, proliferation, DNA damage repair and stem cell-ness, have a prognostic value in advanced stage HNSCC patients when assessed individually. Here we aimed to evaluate and validate this in a multifactorial context and assess interrelation and the combined role of these biological factors in determining chemo-radiotherapy response in HPV-negative advanced HNSCC. Methods: RNA sequencing data of pre-treatment biopsy material from 197 HPV-negative advanced stage HNSCC patients treated with definitive chemoradiotherapy was analyzed. Biological parameter scores were assigned to patient samples using previously generated and described gene expression signatures. Locoregional control rates were used to assess the role of these biological parameters in radiation response and compared to distant metastasis data. Biological factors were ranked according to their clinical impact using bootstrapping methods and multivariate Cox regression analyses that included clinical variables. Multivariate Cox regression analyses comprising all biological variables were used to define their relative role among all factors when combined. Results: Only few biomarker scores correlate with each other, underscoring their independence. The different biological factors do not correlate or cluster, except for the two stem cell markers CD44 and SLC3A2 (r = 0.4, p < 0.001) and acute hypoxia prediction scores which correlated with T-cell infiltration score, CD8 + T cell abundance and proliferation scores (r = 0.52, 0.56, and 0.6, respectively with p < 0.001). van der Heijden et al. HNSCC Biology Impacting Chemo-Radiotherapy Outcomes Locoregional control association analyses revealed that chronic (Hazard Ratio (HR) = 3.9) and acute hypoxia (HR = 1.9), followed by stem cell-ness (CD44/SLC3A2; HR = 2.2/2.3), were the strongest and most robust determinants of radiation response. Furthermore, multivariable analysis, considering other biological and clinical factors, reveal a significant role for EGFR expression (HR = 2.9, p < 0.05) and T-cell infiltration (CD8 + T-cells: HR = 2.2, p < 0.05; CD8 + T-cells/Treg: HR = 2.6, p < 0.01) signatures in locoregional control of chemoradiotherapy-treated HNSCC. Conclusion: Tumor acute and chronic hypoxia, stem cell-ness, and CD8 + Tcell parameters are relevant and largely independent biological factors that together contribute to locoregional control. The combined analyses illustrate the additive value of multifactorial analyses and support a role for EGFR expression analysis and immune cell markers in addition to previously validated biomarkers. This external validation underscores the relevance of biological factors in determining chemoradiotherapy outcome in HNSCC.

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Section: Discussionmentioning

confidence: 99%

Biological Determinants of Chemo-Radiotherapy Response in HPV-Negative Head and Neck Cancer: A Multicentric External Validation

et al. 2020

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“…Accumulation of CTLA-4+ T reg cells in the HPV-positive HNSCC tumor microenvironment [107] and in the peripheral blood of advanced cervical cancer [108] patients, suggests a repressive role for CTLA-4 during HPV infection. The clinical benefits of blocking the CTLA-4 immune inhibitory pathway is also under clinical evaluation in cervical cancer [109] and HNSCC patients [110] .…”

Section: Chronic Hpv Infection Immunoregulatory Cytokine Milieu and mentioning

confidence: 99%

“…Pre-clinical studies have also demonstrated that the combination of HPV16 E7 DNA-based therapeutic vaccines with co-blockade of PD-1/PD-L1 signaling in E6- and E7-expressing transplantable TC-1 tumor bearing mice can significantly enhance the tumor -specific CTL response and improve tumor regression [134] , [135] , [136] . Currently, there are several clinical trials targeting blockade of PD-1/PD-L1 in HNSCCs and nivolumab (anti-PD1 antibody) has been approved by the FDA for the treatment of recurrent or metastatic HNSCC patients [110] , [137] . However, although pembrolizumab [138] and nivolumab [139] anti-PD-1 monoclonal antibodies are under phase I/II trials for the treatment of cervical and other anogenital cancers, it remains to be determined if these strategies can offer a therapeutic advantage for clearance of HPV-related tumors in patients.…”

Section: Chronic Hpv Infection Immunoregulatory Cytokine Milieu and mentioning

confidence: 99%

Modulation of antigen presenting cell functions during chronic HPV infection

Bashaw

Leggatt

Chandra

et al. 2017

Papillomavirus Research

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High-risk human papillomaviruses (HR-HPV) infect basal keratinocytes, where in some individuals they evade host immune responses and persist. Persistent HR-HPV infection of the cervix causes precancerous neoplasia that can eventuate in cervical cancer. Dendritic cells (DCs) are efficient in priming/cross-priming antigen-specific T cells and generating antiviral and antitumor cytotoxic CD8+ T cells. However, HR-HPV have adopted various immunosuppressive strategies, with modulation of DC function crucial to escape from the host adaptive immune response. HPV E6 and E7 oncoproteins alter recruitment and localization of epidermal DCs, while soluble regulatory factors derived from HPV-induced hyperplastic epithelium change DC development and influence initiation of specific cellular immune responses. This review focuses on current evidence for HR-HPV manipulation of antigen presentation in dendritic cells and escape from host immunity.

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“…On the one hand, tumor infiltrating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells eliminate the tumor cells and limit the tumor progression(Ferris, ). On the other hand, immunosuppressive cells, such as myeloid derived suppressor cells (MDSCs), tumor‐associated macrophages (TAMs), and regulatory T cells (Tregs), facilitate the tumor evasion and enhance the tumor progression(Dogan, Rieckmann, Munscher, & Busch, ). Based on the close relationship between immune status and HNSCC, immunotherapy has aroused extensive attention for HNSCC treatment.…”

Section: Introductionmentioning

confidence: 99%

Co‐inhibitory immune checkpoints in head and neck squamous cell carcinoma

Deng

Sun

2018

Oral Diseases

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The upregulation of co-inhibitory immune checkpoints hampers the immune response toward tumor cells and facilitates the tumor cells ability to evade immunosurveillance. Specific inhibitory immune checkpoint delivers inhibitory signals to T cells using multiple mechanisms. More in-depth understanding of the co-inhibitory immune checkpoints could be exploited for head and neck squamous cell carcinoma (HNSCC) treatment. In this review, we summarize the expression and the mechanism of partial co-inhibitory immune checkpoint signals and discuss targeting co-inhibitory immune checkpoints as an immunotherapeutic target for cancer therapy. This review may provide a better understanding of the co-inhibitory immune checkpoints and could promote applications of immunotherapy.

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Current studies of immunotherapy in head and neck cancer

Cited by 60 publications

References 31 publications

Biological Determinants of Chemo-Radiotherapy Response in HPV-Negative Head and Neck Cancer: A Multicentric External Validation

Biological Determinants of Chemo-Radiotherapy Response in HPV-Negative Head and Neck Cancer: A Multicentric External Validation

Modulation of antigen presenting cell functions during chronic HPV infection

Co‐inhibitory immune checkpoints in head and neck squamous cell carcinoma

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