The 5-Ws of immunotherapy in head and neck cancer

Botticelli, Andrea; Mezi, Silvia; Pomati, Giulia; Cerbelli, Bruna; Rocco, Christiana Di; Amirhassankhani, Sasan; Sirgiovanni, Grazia; Occhipinti, Mario; Napoli, Valerio Maria; Emiliani, Alessandra; Mazzuca, Federica; Tomao, Silverio; Nuti, Marianna; Marchetti, Paolo

doi:10.1016/j.critrevonc.2020.103041

Cited by 15 publications

(12 citation statements)

References 123 publications

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“…These changes have been linked to alterations in the TME [37][38][39][40]. In HNSCC, an immune suppressive equilibrium has been identified, which is characterized by a low frequency of dysfunctional immune effector cells and an altered expression of immune modulatory molecules of HNSCC cells [41]. In HPV + HNSCC, the distinct underlying immune escape mechanisms have been well identified [7,42], while there is still a lack of data concerning immune evasion of HPV -OSCC lesions.…”

Section: Discussionmentioning

confidence: 99%

Tumor Microenvironment, HLA Class I and APM Expression in HPV-Negative Oral Squamous Cell Carcinoma

Wickenhauser¹,

Bethmann²,

Kappler³

et al. 2021

Preprint

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Progression of oral squamous cell carcinoma (OSCC) has been associated with an escape of tumor cells from the host immune surveillance due to an increased knowledge of its underlying molecular mechanisms and its modulation by the tumor microenvironment and immune cell repertoire. In this study the expression of HLA class I (HLA-I) antigens and of components of the antigen processing machinery (APM) was analyzed in 160 pathologically classified human papilloma virus (HPV)-negative OSCC lesions and correlated to the intra-tumoral immune cell response, IFN- signaling and to the patients outcome. A heterogeneous, but predominantly lower constitutive protein expression of HLA-I APM components was found in OSCC sections when compared to non-neoplastic cells. Tumoral HLA-I APM component expression was further categorized into the three major phenotypes HLA-Ihigh/APMhigh, HLA-Ilow/APMlow and HLA-Idiscordant high/low/APMhigh. In the HLA-Ihigh/APMhigh group, the highest frequency of intra-tumoral CD8+ T cells and lowest number of CD8+ T cells close to FoxP3+ cells was found. Patients within this group presented the most unfavorable survival, which was significantly evident in stage T2 tumors. Despite a correlation with the number of intra-tumoral CD8+ T cells, tumoral JAK1 expression as a surrogate marker for IFN- signaling was not associated with HLA-I/APM expression. Thus, the presented findings strongly indicate the presence of additional factors involved in the immunomodulatory process of HPV-negative OSCC with a possible tumor-burden-dependent complex network of immune escape mechanisms beyond HLA-I/APM components and T cell infiltration in this tumor entity.

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Section: Discussionmentioning

confidence: 99%

Tumor Microenvironment, HLA Class I and APM Expression in HPV-Negative Oral Squamous Cell Carcinoma

Wickenhauser¹,

Bethmann²,

Kappler³

et al. 2021

Preprint

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“…It has become evident that an altered expression pattern of HLA-I antigens and HLA-I APM components in tumors represents an important immune escape mechanism from CTLmediated elimination in distinct tumor types, which is frequently associated with poor prognosis and resistance to immunotherapy, and has been linked to changes in the TME [37][38][39][40]. In HNSCC, an immune suppressive equilibrium has been identified, which is characterized by a low frequency of dysfunctional immune effector cells and an altered expression of immune modulatory molecules of HNSCC cells [41]. In HPV + HNSCC, the distinct underlying immune escape mechanisms have been well identified [7,42], while there is still a lack of data concerning immune evasion of HPV -OSCC lesions.…”

Section: Discussionmentioning

confidence: 99%

Tumoral HLA Class I and APM Expression and Its Effect on Intratumoral T-cell Reaction and Outcome in HPV-Negative Oral Squamous Cell Carcinoma

Wickenhauser¹,

Bethmann²,

Kappler³

et al. 2020

Preprint

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Progression of oral squamous cell carcinoma (OSCC) has been associated with an escape of tumor cells from the host immune surveillance with growing evidence of its underlying molecular mechanisms and its interaction with the immune cell control. In this study the expression of HLA class I (HLA-I) antigens and of components of the antigen processing machinery (APM) was analyzed in 160 consecutive human papilloma virus (HPV)-negative OSCC lesions and correlated to tumor specific parameters, the intratumoral immune cell response and to the patients outcome. A heterogeneous, but predominantly lower constitutive protein expression of HLA-I APM components was seen in OSCC sections when compared to non-neoplastic cells. Based on the expression levels of HLA-I APM components three main OSCC subgroups were detected and categorized into HLA-Ihigh/APMhigh, HLA-Ilow/APMlow and HLA-Idiscordant high/low/APMhigh phenotypes. In the HLA-Ihigh/APMhigh group, the highest frequency of intratumoral CD8+ T cells and lowest number of CD8+ T cells close to FoxP3 cells was found. Despite being associated with the highest T cell infiltration, patients within this group presented the most unfavorable survival, which was most evident in stage T2 tumors. Thus, the presented findings strongly indicate the presence of additional factors involved in the immunomodulatory process of HPV-negative OSCC with a possible tumor-burden-dependent complex network of immune escape mechanisms beyond HLA-I/APM components and T cell infiltration in this tumor entity.

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“…In metastatic SCCHN, prior to the integration of immunotherapy, first-line systemic therapies consisted of a combination of cytotoxic agents with cetuximab, a chimeric IgG1 monoclonal antibody targeting human EGFR [ 25 , 47 ]. Even though the introduction of immune checkpoint inhibitors (ICIs) has revolutionized the treatment of recurrent or metastatic disease [ 48 ], most patients still succumb to their disease, and novel therapeutic combinatorial approaches are urgently needed.…”

Section: The Prospects Of Combination Of Vegf Inhibitors With Immunot...mentioning

confidence: 99%

Targeting Angiogenesis in Squamous Cell Carcinoma of the Head and Neck: Opportunities in the Immunotherapy Era

Saba

Vijayvargiya

Vermorken

et al. 2022

Cancers

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Despite the lack of approved anti-angiogenic therapies in squamous cell carcinoma of the head and neck (SCCHN), preclinical and more recent clinical evidence support the role of targeting the vascular endothelial growth factor (VEGF) in this disease. Targeting VEGF has gained even greater interest following the recent evidence supporting the role of immunotherapy in the management of advanced SCCHN. Preclinical evidence strongly suggests that VEGF plays a role in promoting the growth and progression of SCCHN, and clinical evidence exists as to the value of combining this strategy with immunotherapeutic agents. Close to 90% of SCCHNs express VEGF, which has been correlated with a worse clinical prognosis and an increased resistance to chemotherapeutic agents. As immunotherapy is currently at the forefront of the management of advanced SCCHN, revisiting the rationale for targeting angiogenesis in this disease has become an even more attractive proposition.

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The 5-Ws of immunotherapy in head and neck cancer

Cited by 15 publications

References 123 publications

Tumor Microenvironment, HLA Class I and APM Expression in HPV-Negative Oral Squamous Cell Carcinoma

Tumor Microenvironment, HLA Class I and APM Expression in HPV-Negative Oral Squamous Cell Carcinoma

Tumoral HLA Class I and APM Expression and Its Effect on Intratumoral T-cell Reaction and Outcome in HPV-Negative Oral Squamous Cell Carcinoma

Targeting Angiogenesis in Squamous Cell Carcinoma of the Head and Neck: Opportunities in the Immunotherapy Era

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