Mononuclear phagocyte system-related multi-omics features yield head and neck squamous cell carcinoma subtypes with distinct overall survival, drug, and immunotherapy responses
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ABSTRACT:
SUBMITTER: Zhang C
PROVIDER: S-EPMC10817853 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Mitophagy serves as a critical mechanism for tumor cell death, significantly impacting the progression of tumors and their treatment approaches. There are significant challenges in treating patients with head and neck squamous cell carcinoma, underscoring the importance of identifying new targets for therapy. The function of mitophagy in head and neck squamous carcinoma remains uncertain, thus investigating its impact on patient outcomes and immunotherapeutic responses is especially crucial. We initially analyzed the differential expression, prognostic value, intergene correlations, copy number variations, and mutation frequencies of mitophagy-related genes at the pan-cancer level. Through unsupervised clustering, we divided head and neck squamous carcinoma into three subtypes with distinct prognoses, identified the signaling pathway features of each subtype using ssGSEA, and characterized subtype B as having features of an immune desert using various immune infiltration calculation methods. Using multi-omics data, we identified the genomic variation characteristics, mutated gene pathway features, and drug sensitivity features of the mitophagy subtypes. Utilizing a combination of 10 machine learning algorithms, we have developed a prognostic scoring model called Mitophagy Subgroup Risk Score (MSRS), which is used to predict patient survival and the response to immune checkpoint blockade therapy. Simultaneously, we applied MSRS to single-cell analysis to explore intercellular communication. Through laboratory experiments, we validated the biological function of SLC26A9, one of the genes in the risk model. In summary, we have explored the significant role of mitophagy in head and neck tumors through multi-omics data, providing new directions for clinical treatment.
| S-EPMC11236326 | biostudies-literature
Project description:PURPOSE OF REVIEW:Discussion of current strategies targeting the immune system related to solid tumors with emphasis on head and neck squamous cell carcinoma (HNSCC).This review will outline the current challenges with immunotherapy and future goals for treatment using these agents. RECENT FINDINGS:Agents targeting immune checkpoint receptors (IR) such as program death 1 (PD1) have been used in the clinical realm for melanoma and non-small cell lung cancer (NSCLC), and the use of these agents for these malignancies has provided crucial information about how and why patients respond or not to inhibitory checkpoint receptor blockade therapy (ICR). The anti PD1 agent, nivolumab, was recently approved by the FDA as a standard of care regimen for patients with platinum refractory recurrent/metastatic (R/M) HNSCC. Molecular pathways leading to resistance are starting to be identified, and work is underway to understand the most optimal treatment regimen with incorporation of immunotherapy. ICR has renewed interest in the immunology of cancer, but resistance is not uncommon, and thus understanding of these mechanisms will allow the clinician to appropriately select patients that will benefit from this therapy.
| S-EPMC5835060 | biostudies-literature
Project description:Prognosis in relapsed metastatic head and neck squamous cell cancer (RM-HNSCC) is dismal. Platinum based chemotherapy in combination with Cetuximab is used in first-line setting, while no further validated options are available at progression. Immunotherapy has produced durable clinical benefit in some patients with RM-HNSCC although the premises are several patients are nonresponders. Studies are ongoing to determine predictive factors and the ideal setting/combination of novel immunotherapies. In this paper, we discuss the past and present of immunotherapy in head and neck cancer and provide an up-to-date information regarding the potential ways to improve immunotherapy outcomes in HNSCC.
| S-EPMC6222190 | biostudies-literature
Project description:BackgroundGrowing evidence indicates that abnormal liquid-liquid phase separation (LLPS) can disrupt biomolecular condensates, contributing to cancer development and progression. However, the influence of LLPS on the prognosis of head and neck squamous cell carcinoma (HNSCC) patients and its effects on the tumor immune microenvironment (TIME) are not yet fully understood. Therefore, we aimed to categorize patients with HNSCC based on LLPS-related genes and explored their multidimensional heterogeneity.MethodsWe integrated the transcriptomic data of 3,541 LLPS-related genes to assess the LLPS patterns in 501 patients with HNSCC within The Cancer Genome Atlas cohort. Subsequently, we explored the differences among the three LLPS subtypes using multi-omics analysis. We also developed an LLPS-related prognostic risk signature (LPRS) to facilitate personalized and integrative assessments and then screened and validated potential therapeutic small molecule compounds targeting HNSCC via experimental analyses.ResultBy analyzing the expression profiles of 85 scaffolds, 355 regulators, and 3,101 clients of LLPS in HNSCC, we identified three distinct LLPS subtypes: LS1, LS2, and LS3. We confirmed notable differences among these subtypes in terms of prognosis, functional enrichment, genomic alterations, TIME patterns, and responses to immunotherapy. Additionally, we developed the LPRS, a prognostic signature for personalized integrative assessments, which demonstrated strong predictive capability for HNSCC prognosis across multiple cohorts. The LPRS also showed significant correlations with the clinicopathological features and TIME patterns in HNSCC patients. Furthermore, the LPRS effectively predicted responses to immune checkpoint inhibitor therapy and facilitated the screening of potential small-molecule compounds for treating HNSCC patients.ConclusionThis study presents a new classification system for HNSCC patients grounded in LLPS. The LPRS developed in this research offers improved personalized prognosis and could optimize immunotherapy strategies for HNSCC.
| S-EPMC11897011 | biostudies-literature
Project description:To show the relationship between antibody delivery and therapeutic efficacy in head and neck cancers, in this study we evaluated the pharmacokinetics and pharmacodynamics of epidermal growth factor receptor (EGFR)-targeted immunotherapy and radioimmunotherapy by quantitative positron emission tomography (PET) imaging.EGFR expression on UM-SCC-22B and SCC1 human head and neck squamous cell cancer (HNSCC) cells were determined by flow cytometry and immunostaining. Tumor delivery and distribution of cetuximab in tumor-bearing nude mice were evaluated with small animal PET using (64)Cu-DOTA-cetuximab. The in vitro toxicity of cetuximab to HNSCC cells was evaluated by MTT assay. The tumor-bearing mice were then treated with four doses of cetuximab at 10 mg/kg per dose, and tumor growth was evaluated by caliper measurement. FDG PET was done after the third dose of antibody administration to evaluate tumor response. Apoptosis and tumor cell proliferation after cetuximab treatment were analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Ki-67 staining. Radioimmunotherapy was done with (90)Y-DOTA-cetuximab.EGFR expression on UM-SCC-22B cells is lower than that on SCC1 cells. However, the UM-SCC-22B tumors showed much higher (64)Cu-DOTA-cetuximab accumulation than the SCC1 tumors. Cetuximab-induced apoptosis in SCC1 tumors and tumor growth was significantly inhibited, whereas an agonistic effect of cetuximab on UM-SCC-22B tumor growth was observed. After cetuximab treatment, the SCC1 tumors showed decreased FDG uptake, and the UM-SCC-22B tumors had increased FDG uptake. UM-SCC-22B tumors are more responsive to (90)Y-DOTA-cetuximab treatment than SCC1 tumors, partially due to the high tumor accumulation of the injected antibody.Cetuximab has an agonistic effect on the growth of UM-SCC-22B tumors, indicating that tumor response to cetuximab treatment is not necessarily related to EGFR expression and antibody delivery efficiency, as determined by PET imaging. Although PET imaging with antibodies as tracers has limited function in patient screening, it can provide guidance for targeted therapy using antibodies as delivery vehicles.
| S-EPMC2848903 | biostudies-other
Project description:The immune system plays an important role in the evolution of malignancy and has become an important target for novel antineoplastic agents. This review article focuses on key features of tumor immunology, including the role of immunotherapy in general and as it pertains to head and neck squamous cell carcinoma. Side effects, resistance mechanisms, and therapeutic monitoring strategies pertaining to immunotherapy are discussed.
| S-EPMC6728550 | biostudies-literature
Project description:Human papilloma virus (HPV) associated oropharynx carcinoma (OPC) is increasingly common, with a distinct biology from HPV negative OPC. In spite of this better prognosis, morbidity is significant and treatment related after effects can be debilitating. Because the foreign viral proteins that drive HPV+ cancers are known, there are multiple options for tailored immune therapies. Herein we review the immunologic basis for disease and emerging immune therapies. The oncogenesis of HPV+ SCCHN goes beyond cell cycle deregulation, and relies on the immune escape through (E5, E6, and E7) downregulating antigen processing, interferon response, as well as STAT-1 signaling. Individual susceptibilities to HPV infection may vary. The treatment of HPV+ cancers has had a wide range of successes and failures. Perhaps the shining example of immunoprevention has been the L1 protein vaccines developed for cervical cancer prevention, however this vaccine has not been beneficial for people already infected. Therefore multiple strategies have been employed in the cancer therapeutic realm for people with existing disease. These agents range from peptides, to viral vectors, to adoptive cell therapy. In this review we consider the work done in both SCCHN and cervical cancer, as these therapeutic targets are the similar. The listed studies are not exhaustive, but rather illustrate experimental design and approach.
| S-EPMC4437525 | biostudies-literature
Project description:Background/purposeHead and neck squamous cell carcinoma (HNSCC) is a serious disease endangering the health of patients, and the application of immunotherapy in HNSCC is gradually emerging. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hotspots of immunotherapy for HNSCC.Materials and methodsPublications related to immunotherapy for HNSCC from 2002 to 2021 were searched in the Web of Science Core Collection database. The software VOSviewers, CiteSpace, and the R package 'bibliometrix' were used to perform this bibliometric analysis.ResultsA total of 1297 publications were from 63 countries, led by the USA and China. The number of publications related to immunotherapy for HNSCC has increased rapidly from 2015. University of Pittsburgh and The University of Texas M.D. Anderson Cancer Center are the main research institutions. Oral Oncology is the most popular journal in this field, and the Journal of Clinical Oncology is the most highly co-cited journal. These publications were from 7569 authors, with Robert L. Ferris publishing the most papers and being the most frequently co-cited. Clinical trials related to nivolumab and pembrolizumab have attracted wide attention. 'Immune checkpoint inhibitors', 'human papillomavirus', 'programmed cell death-ligand 1', and 'programmed cell death protein 1' are the main keywords of emerging research hotspots.ConclusionThis study presents a comprehensive summary of the trends and development of immunotherapy for HNSCC, identifies the research frontier and hotspot direction, and could provide a valuable reference for researchers in this field.
| S-EPMC10068494 | biostudies-literature
Project description:ObjectiveProvide a narrative review of the literature describing immunological concepts and novel approaches in the treatment of head and neck squamous cell carcinoma.BackgroundIn 2016, two anti-PD1 antibodies, nivolumab and pembrolizumab, were shown to improve overall survival in patients with recurrent/metastatic HNSCC and were approved by the US Food and Drug Administration (FDA) for use in the second line, cisplatin-resistant setting, although the overall response rates were only about 15%. More recently, pembrolizumab was approved for use in the first-line R/M setting as monotherapy in patients with CPS >1 or in combination with chemotherapy regardless of PD-L1 expression. Interestingly, while response rates with combination therapy were increased compared to pembrolizumab alone, the duration of response was shorter than might be expected. Based on a growing amount of evidence in other types of cancer treated with various combinations of immunotherapy, similar concepts are being studied in HNSCC, both in pre-clinical models and in clinical trials.MethodsA review of the literature was conducted using the Medline-PubMed and ClinicalTrials.gov databases. Main topics were selected for review, including basic immunology background, checkpoint inhibition, neoadjuvant immunotherapy, the combination of immunotherapy with radiation therapy and chemotherapy, intratumoral immunotherapy, and future prospects.ConclusionsThere is an ongoing effort, which is supported by an increasing body of evidence, to enhance response rates with combinations of immunotherapy with other immunotherapy agents, targeted small molecules, chemotherapy, radiation therapy, and surgery. The clinician and the scientist should be familiarized with basic immunologic concepts, key findings in recent clinical trials, and current indications for administering immunotherapy.
| S-EPMC9469879 | biostudies-literature
Project description:The immune system plays a fundamental role in preventing cancer development by recognising and eliminating tumour cells. The recent success in the field of immunotherapy has confirmed the potential to exploit the immune response as a cancer treatment. Head and neck squamous cell carcinoma (HNSCC) is a malignancy characterized by dismal prognosis and high mortality rate; low survival outcomes in combination with significant toxicity of current treatment strategies highlight the necessity for novel therapeutic modalities. HNSCC is a favourable disease for immunotherapy, as immune escape plays a key role in tumour initiation and progression. T-cell checkpoint inhibitors targeting programmed cell death protein-1 have emerged as novel immunotherapy agents showing remarkable efficacy in HNSCC. However, only a minority of patients derive benefit for single-agent immunotherapies. In this regard, combinatorial immunotherapy approaches represent an alternative strategy that might increase the number of patients who respond to immunotherapy. Focusing on HNSCC, this review will summarise novel combinations of immune checkpoint blockade with other immunotherapy treatment modalities.
| S-EPMC5548974 | biostudies-literature