Immunotherapy and Checkpoint Inhibitors in Recurrent and Metastatic Head and Neck Cancer

Hashemi-Sadraei, Nooshin; Sikora, Andrew G.; Brizel, David M.

doi:10.14694/edbk_157801

Cited by 11 publications

(5 citation statements)

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“…Many ongoing studies are exploring the effect of immune checkpoint inhibitors in recurrent and metastatic HNSCC, which include single agent and combination of immune checkpoint inhibitors as dual inhibition, combination with chemotherapy, radiotherapy, targeted agents as well as immunomodulators. 25 Here, our results demonstrated that LAG-3 was upregulated in recurrent HNSCC, metastatic lymph nodes and HNSCC with pre-radiotherapy. These findings provided a potential immunotherapeutic rationale that the efficiency of LAG-3 blockade coupled with or without radiotherapy should be evaluated in recurrent or metastatic HNSCC.…”

Section: Discussionsupporting

confidence: 55%

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LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma

et al. 2016

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Immunotherapy with immune checkpoint molecule-specific monoclonal antibody have obtained encouraging results from preclinical studies and clinical trials, which promoted us to explore whether this kind of immunotherapy could be applicable to head and neck squamous cell carcinoma (HNSCC). Lymphocyte activation gene-3 (LAG-3) is an immune checkpoint control protein that negatively regulates T cells and immune response. Here, using the human tissue samples, we report these findings that LAG-3 is overexpressed on tumorinfiltrating lymphocytes (TILs; p < 0.001) and its overexpression correlates with the high pathological grades, lager tumor size and positive lymph node status in human primary HNSCC. Survival analysis identifies LAG-3 as a prognostic factor independent of tumor size and pathological grades for primary HNSCC patients with negative lymph node status (p D 0.014). Study in immunocompetent genetically defined HNSCC mouse model reports that LAG-3 is upregulated on CD4 C T cells, CD8 C T cells and CD4 C Foxp3 C regulatory T cells (Tregs). In vivo study, administration of LAG-3-specific antibody retards tumor growth in a way associated with enhanced systemic antitumor response by potentiating the antitumor response of CD8 C T cells and decreasing the population of immunosuppressive cells. Taken together, our results offer a preclinical proof supporting the immunomodulatory effects of LAG-3 and suggest a potential therapeutic target of immunotherapy for HNSCC.

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Section: Discussionsupporting

confidence: 55%

“…25 Immunotherapy for HNSCC disrupting PD-1/PD-L1 axis has yielded encouraged responses, which seem to be durable in patients with refractory disease. 25 In the present study, the expression of LAG-3 significantly increased in recurrent HNSCC (RH, n D 8, p < 0.001; Fig. 1C), metastatic lymph nodes (LN, n D 41, p < 0.001; Fig.…”

Section: Resultsmentioning

confidence: 99%

LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma

et al. 2016

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“…Hence, a diminished CTLA-4 level maintains inflammatory reactions. Similarly, PD-1 is expressed on the surface of T-cells upon activation and is involved in limiting inflammatory reactions ( 21 ). Its ligand, PD-1L, can be found on tumor cells and provokes upregulation of PD-1 in T cells.…”

Section: Discussionmentioning

confidence: 99%

Coexistence of sarcoidosis and metastatic lesions: A diagnostic and therapeutic dilemma (Review)

Spiekermann¹,

Kuhlencord²,

Huss³

et al. 2017

Oncol Lett

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Sarcoidosis, a chronic, inflammatory disease that affects various different organs, is characterized by noncaseating epitheloid granulomas. This systemic inflammatory process is associated with an increased risk of cancer. Several cases of sarcoidosis that mimic metastatic tumor progression in radiological findings have been reported so far. However, there are also cases that have presented a coexistence of sarcoidosis and metastasis, which have caused a diagnostic and therapeutic dilemma. Due to inadequate current therapies, a reliable differentiation between benign and malignant lesions is crucial. This review focuses on the residual risk of the coexistence of metastases within radiological suspicious lesions in patients with a history of solid tumors and sarcoidosis, as well as immunological findings, in order to explain the potential associations. Sarcoidosis has the potential to promote metastasis as it includes tumor-promoting and immune-regulating cell subsets. Notably, myeloid derived suppressor cells may serve a pivotal role in metastatic progression in patients with sarcoidosis. In addition, the present review also evaluates the potential novel diagnostic approaches, which may be able to differentiate between metastatic lesions and sarcoidosis. The risk of coexistent metastasis in sarcoidosis lesions must be considered by clinical practitioners, and a multidisciplinary approach may be required to avoid misdiagnosis and the subsequent unnecessary surgery or insufficient treatments.

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“…Immune surveillance is an important mechanism to prevent progression of HNSCC. The cancer cells can evade the immune system through multiple mechanisms including T‐cell tolerance, and inhibition of T cell‐related pathways via co‐receptors commonly known as immune checkpoints 57. These checkpoints are negative co‐stimulatory ligands expressed on tumor and infiltrating cells that bind receptors expressed on tumor infiltrating T‐cells that functionally suppress T‐cell function and induce T‐cell apoptosis 58.…”

Section: Resultsmentioning

confidence: 99%

Genomics and advances towards precision medicine for head and neck squamous cell carcinoma

Waes

Musbahi

2017

Laryngoscope Investig Oto

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ObjectiveTo provide a review of emerging knowledge from genomics and related basic science, preclinical, and clinical precision medicine studies in head and neck squamous cell carcinoma (HNSCC).Data SourcesThe Cancer Genome Atlas Network (TCGA) publications, PubMed‐based literature review, and ClinicalTrials.gov.Review MethodsTCGA publications, PubMed, and ClinicalTrials.gov were queried for genomics and related basic science, preclinical, and developmental clinical precision medicine studies in HNSCC.ResultsTCGA reported comprehensive genomic analyses of 279 HNSCC, defining the landscape and frequency of chromosomal copy number alterations, mutations, and expressed genes that contribute to pathogenesis, prognosis, and resistance to therapy. This provides a road map for basic science and preclinical studies to identify key pathways in cancer and cells of the tumor microenvironment affected by these alterations, and candidate targets for new small molecule and biologic therapies.ConclusionRecurrent chromosomal abnormalities, mutations, and expression of genes affecting HNSCC subsets are associated with differences in prognosis, and define molecules, pathways, and deregulated immune responses as candidates for therapy. Activity of molecularly targeted agents appears to be enhanced by rational combinations of these agents and standard therapies targeting the complex alterations that affect multiple pathways and mechanisms in HNSCC.Level of EvidenceNA.

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Immunotherapy and Checkpoint Inhibitors in Recurrent and Metastatic Head and Neck Cancer

Cited by 11 publications

References 0 publications

LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma

LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma

Coexistence of sarcoidosis and metastatic lesions: A diagnostic and therapeutic dilemma (Review)

Genomics and advances towards precision medicine for head and neck squamous cell carcinoma

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