Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Immune deserts in head and neck squamous cell carcinoma: A review of challenges and opportunities for modulating the tumor immune microenvironment.

ABSTRACT: Immunotherapy revolutionized cancer treatment but has yet to elicit durable responses in the majority of patients with head and neck squamous cell carcinoma (HNSCC). HNSCC is generally characterized by a high tumor mutational burden, which has translated to a large neoantigen load that could prime the immune system to recognize and eliminate malignant cells. Studies are increasingly showing, however, that HNSCC is an "immune desert" tumor that can hijack multiple parts of the tumor immunity cycle in order to evade immune recognition and suppress immune system activation. Herein we will review how HNSCC tumors modulate their architecture, cellular composition, and cytokine milieu to maximize immunosuppression; as well as relevant therapeutic opportunities and emerging issues facing the field of HNSCC immuno-oncology.

SUBMITTER: Farlow JL

PROVIDER: S-EPMC8753751 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Immune deserts in head and neck squamous cell carcinoma: A review of challenges and opportunities for modulating the tumor immune microenvironment.

Farlow Janice L JL Brenner J Chad JC Lei Yu L YL Chinn Steven B SB

Oral oncology 20210701

Immunotherapy revolutionized cancer treatment but has yet to elicit durable responses in the majority of patients with head and neck squamous cell carcinoma (HNSCC). HNSCC is generally characterized by a high tumor mutational burden, which has translated to a large neoantigen load that could prime the immune system to recognize and eliminate malignant cells. Studies are increasingly showing, however, that HNSCC is an "immune desert" tumor that can hijack multiple parts of the tumor immunity cycl ...[more]

PMID: 34218062

Similar Datasets

Heterogeneity of cancer-associated fibroblasts in head and neck squamous cell carcinoma: opportunities and challenges.

Project description:Head and neck squamous cell carcinoma (HNSCC) is among the most severe and complex malignant diseases with a high level of heterogeneity and, as a result, a wide range of therapeutic responses, regardless of clinical stage. Tumor progression depends on ongoing co-evolution and cross-talk with the tumor microenvironment (TME). In particular, cancer-associated fibroblasts (CAFs), embedded in the extracellular matrix (ECM), induce tumor growth and survival by interacting with tumor cells. Origin of CAFs is quite varied, and the activation patterns of CAFs are also heterogeneous. Crucially, the heterogeneity of CAFs appears to play a key role in ongoing tumor expansion, including facilitating proliferation, enhancing angiogenesis and invasion, and promoting therapy resistance, through the production of cytokines, chemokines, and other tumor-promotive molecules in the TME. This review describes the various origin and heterogeneous activation mechanisms of CAFs, and biological heterogeneity of CAFs in HNSCC is also included. Moreover, we have highlighted versatility of CAFs heterogeneity in HNSCC progression, and have discussed different tumor-promotive functions of CAFs respectively. In the future, it is a promising strategy for the therapy of HNSCC that specifically targeting tumor-promoting CAF subsets or the tumor-promoting functional targets of CAFs.

| S-EPMC10102018 | biostudies-literature

Tumor microenvironment and immune-related therapies of head and neck squamous cell carcinoma.

Project description:Head and neck squamous cell carcinomas (HNSCCs) are a type of common malignant tumor, mainly manifesting as oropharyngeal, oral cavity, laryngopharyngeal, hypopharyngeal, and laryngeal cancers. These highly aggressive malignant tumors reportedly affect more than 830,000 patients worldwide every year. Currently, the main treatments for HNSCC include surgery, radiotherapy, chemotherapy, and immunotherapy, as well as combination therapy. However, the overall 5-year survival rate of HNSCC has remained 50%, and it has not significantly improved in the past 10 years. Previous studies have shown that the tumor microenvironment (TME) plays a crucial role in the recurrence, metastasis, and drug resistance of patients with HNSCC. In this review, we summarize the role of anti-tumor and pro-tumor immune cells, as well as extracellular components in the TME of HNSCC. We also discuss classical HNSCC immunotherapy and highlight examples of clinical trials using CTLA-4 inhibitors and programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1)-related combination therapies. We also outline some molecules in the TME known to regulate immunosuppressive cells. Furthermore, the role and underlying mechanism of radiation therapy on the TME, immune cells, and immune response are discussed.

| S-EPMC7878981 | biostudies-literature

The Immune Microenvironment in Head and Neck Squamous Cell Carcinoma: on Subsets and Subsites.

Project description:PURPOSE:To understand why some patients respond to immunotherapy but many do not, a clear picture of the tumor microenvironment (TME) of head and neck squamous cell carcinoma (HNSCC) is key. Here we review the current understanding on the immune composition per HNSCC subsite, the importance of the tumor's etiology and the prognostic power of specific immune cells. RECENT FINDINGS:Large cohort data are mostly based on deconvolution of transcriptional databases. Studies focusing on infiltrate localization often entail small cohorts, a mixture of HNSCC subsites, or focus on a single immune marker rather than the interaction between cells within the TME. Conclusions on the prognostic impact of specific immune cells in HNSCC are hampered by the use of heterogeneous or small cohorts. To move forward, the field should focus on deciphering the immune composition per HNSCC subsite, in powered cohorts and considering the molecular diversity in this disease.

| S-EPMC7324425 | biostudies-literature

Targeting the Immune Microenvironment in the Treatment of Head and Neck Squamous Cell Carcinoma.

Project description:Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive solid tumor, with a 5-year mortality rate of ~50%. The development of immunotherapies has improved the survival of patients with HNSCC, but, the long-term prognosis of patients with recurrent or metastatic HNSCC remains poor. HNSCC is characterized by intratumoral infiltration of regulatory T cells, dysfunctional natural killer cells, an elevated Treg/CD8+ T cell ratio, and increased programmed cell death ligand 1 protein on tumor cells. This leads to an immunocompromised niche in favor of the proliferation and treatment resistance of cancer cells. To achieve an improved treatment response, several potential combination strategies, such as increasing the neoantigens for antigen presentation and therapeutic agents targeting components of the tumor microenvironment, have been explored and have shown promising results in preclinical studies. In addition, large-scale bioinformatic studies have also identified possible predictive biomarkers of HNSCC. As immunotherapy has shown survival benefits in recent HNSCC clinical trials, a comprehensive investigation of immune cells and immune-related factors/cytokines and the immune profiling of tumor cells during the development of HNSCC may provide more insights into the complex immune microenvironment and thus, facilitate the development of novel immunotherapeutic agents.

| S-EPMC6803444 | biostudies-literature

Effects of Tobacco Smoking on the Tumor Immune Microenvironment in Head and Neck Squamous Cell Carcinoma.

Project description:PurposePatients with head and neck squamous cell carcinoma (HNSCC) who actively smoke during treatment have worse survival compared with never-smokers and former-smokers. We hypothesize the poor prognosis in tobacco smokers with HNSCC is, at least in part, due to ongoing suppression of immune response. We characterized the tumor immune microenvironment (TIM) of HNSCC in a retrospective cohort of 177 current, former, and never smokers.Experimental designTumor specimens were subjected to analysis of CD3, CD8, FOXP3, PD-1, PD-L1, and pancytokeratin by multiplex immunofluorescence, whole-exome sequencing, and RNA sequencing. Immune markers were measured in tumor core, tumor margin, and stroma.ResultsOur data indicate that current smokers have significantly lower numbers of CD8+ cytotoxic T cells and PD-L1+ cells in the TIM compared with never- and former-smokers. While tumor mutation burden and mutant allele tumor heterogeneity score do not associate with smoking status, gene-set enrichment analyses reveal significant suppression of IFNα and IFNγ response pathways in current smokers. Gene expression of canonical IFN response chemokines, CXCL9, CXCL10, and CXCL11, are lower in current smokers than in former smokers, suggesting a mechanism for the decreased immune cell migration to tumor sites.ConclusionsThese results suggest active tobacco use in HNSCC has an immunosuppressive effect through inhibition of tumor infiltration of cytotoxic T cells, likely as a result of suppression of IFN response pathways. Our study highlights the importance of understanding the interaction between smoking and TIM in light of emerging immune modulators for cancer management.

| S-EPMC7073297 | biostudies-literature

Further Understanding of the Immune Microenvironment in Head and Neck Squamous Cell Carcinoma: Implications for Prognosis.

Project description:PurposeWe aimed to review the literature on the tumor microenvironment as a key player in tumor growth and anti-cancer treatment responses in head and neck cancer.Patients and methodsWe reviewed the recent literature on this topic, using the following research words: "tumor microenvironment" and "head and neck cancer or neoplasm or head and neck squamous cell carcinoma" and "immune cells" and "stromal cells". A search was conducted on the PubMed website and reports from international meetings, presentations and abstracts.ResultsThe tumor microenvironment is a complex network in which myeloid cells, tumoral cells, growth factors and cytokines are involved in angiogenesis, the extracellular matrix and epithelial-to-mesenchymal transition.ConclusionImmune resistance and rapid tumor growth depend on immunosuppressive and pro-tumoral environments. Further investigations to classify and adequately treat patients with head and neck cancer are required.

| S-EPMC8139676 | biostudies-literature

Immune-Stimulatory Effects of Curcumin on the Tumor Microenvironment in Head and Neck Squamous Cell Carcinoma.

Project description:Curcumin is known to have immune-modulatory and antitumor effects by interacting with more than 30 different proteins. An important feature of curcumin is the inhibition of nuclear factor kappa of activated B-cells (NF-κB). Here, we evaluate the potential of curcumin to reverse the epithelial to mesenchymal transition (EMT) of head and neck squamous cell carcinoma (HNSCC) cells as a part of tumor escape mechanisms. We examined the impact of curcumin on the expression of different pro- and antitumoral chemokines in ex vivo HNSCC tumor tissue and primary macrophage cultures. Further, we evaluated the combinatorial effect of curcumin and toll-like receptor 3 (TLR3) agonist Poly I:C (PIC) on NF-κB inhibition and regulatory T-cell (Treg) attraction. Mesenchymal markers were significantly reduced in cancer specimens after incubation with curcumin, with simultaneous reduction of key transcription factors of EMT, Snail, and Twist. Furthermore, a decrease of the Treg-attracting chemokine CCL22 was observed. Additionally, curcumin-related inhibition of NF-κB nuclear translocation was evident. The combination of PIC with curcumin resulted in further NF-κB inhibition, whereas PIC alone contrarily resulted in NF-κB activation. Furthermore, curcumin was more effective in inhibiting PIC-dependent NF-κB activation and Treg attraction compared to known NF-κB inhibitors BAY 11-7082 or caffeic acid phenethyl ester (CAPE). The presented results show, for the first time, the immune-modulating effects of curcumin in HNSCC, with potent inhibition of the Treg-attracting effects of PIC. Hence, curcumin presents a promising drug in cancer therapy as a supplement to already established treatments.

| S-EPMC8001767 | biostudies-literature

Immune Modulation of Head and Neck Squamous Cell Carcinoma and the Tumor Microenvironment by Conventional Therapeutics.

Project description:Head and neck squamous cell carcinoma (HNSCC) accounts for more than 600,000 cases and 380,000 deaths annually worldwide. Although human papillomavirus (HPV)-associated HNSCCs have better overall survival compared with HPV-negative HNSCC, loco-regional recurrence remains a significant cause of mortality and additional combinatorial strategies are needed to improve outcomes. The primary conventional therapies to treat HNSCC are surgery, radiation, and chemotherapies; however, multiple other targeted systemic options are used and being tested including cetuximab, bevacizumab, mTOR inhibitors, and metformin. In 2016, the first checkpoint blockade immunotherapy was approved for recurrent or metastatic HNSCC refractory to platinum-based chemotherapy. This immunotherapy approval confirmed the critical importance of the immune system and immunomodulation in HNSCC pathogenesis, response to treatment, and disease control. However, although immuno-oncology agents are rapidly expanding, the role that the immune system plays in the mechanism of action and clinical efficacy of standard conventional therapies is likely underappreciated. In this article, we focus on how conventional and targeted therapies may directly modulate the immune system and the tumor microenvironment to better understand the effects and combinatorial potential of these therapies in the context and era of immunotherapy.

| S-EPMC6635035 | biostudies-literature

Challenges in EGFRvIII detection in head and neck squamous cell carcinoma.

Project description:ObjectiveHead and neck squamous cell carcinoma (HNSCC) accounts for more than 5% of all cancers worldwide. The mortality rate of HNSCC has remained unchanged (approximately 50%) over the last few decades. Ubiquitous overexpression of wild type EGFR in many solid tumors has led to the development of EGFR targeted therapies. EGFR can be constitutively activated via several mechanisms including the truncated, EGFR variant III isoform (EGFRvIII). EGFRvIII lacks exons 2-7 and has been reported to be present in up to 20-40% of HNSCC. EGFRvIII has been shown to contribute to cetuximab resistance. The mechanisms leading to EGFRvIII expression in HNSCC are unknown. The present investigation was undertaken to determine the etiology of EGFRvIII in HNSCC.Materials and methodsFixed HNSCC and glioma tissues were analyzed by fluorescence in situ hybridization for EGFR amplification. DNA and RNA from fresh frozen specimens were used to determine the presence of EGFRvIII transcripts and the mechanisms of expression via PCR, RT-PCR and RNA sequencing.ResultsUnlike glioma, EGFRvIII expression in HNSCC did not correlate with EGFR amplification. We found evidence of genomic deletion of the exon 2-7 in 6 of 7 HNSCC cases examined, however, the presence of genomic deletion did not always result in mRNA expression of EGFRvIII. RNA sequencing with automated alignment did not identify EGFRvIII due to microhomology between intron 1 and exon 8. RNA sequencing analyzed by manual alignment methods did not correlate well with RT-PCR and PCR findings.ConclusionThese findings suggest that genomic deletion as well as additional regulatory mechanisms may contribute to EGFRvIII expression in HNSCC. Further, large scale automated alignment of sequencing are unlikely to identify EGFRvIII and an assay specifically designed to detect EGFRvIII may be necessary to detect this altered form of EGFR in HNSCC tumors.

| S-EPMC4320077 | biostudies-literature