Lymphatic-preserving treatment sequencing with immune checkpoint inhibition unleashes cDC1-dependent antitumor immunity in HNSCC

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Июль 25, 2022

Despite the promise of immune checkpoint inhibition (ICI), therapeutic responses remain limited. This raises possibility that standard care treatments delivered in concert may compromise tumor response. To address this, we employ tobacco-signature head and neck squamous cell carcinoma murine models which map tumor-draining lymphatics develop for regional lymphablation with surgery or radiation. We find eliminates ICI response, worsening overall survival repolarizing tumor- peripheral-immune compartments. Mechanistically, within lymphatics, observe an upregulation conventional type I dendritic cells interferon signaling show both are necessary response lost lymphablation. Ultimately, provide a mechanistic understanding how oncologic therapies targeting impact to immune-oncology therapy order define rational, lymphatic-preserving treatment sequences mobilize systemic antitumor immunity, achieve optimal responses, control metastatic disease, confer durable immunity.

Язык: Английский

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Lymph node metastasis in oral squamous cell carcinoma: Where we are and where we are going

Clinical and Translational Discovery, Год журнала: 2023, Номер 3(4)

Опубликована: Авг. 1, 2023

Abstract Background Oral cancer is a common malignant tumour in the head and neck region, with over 90% of cases being oral squamous cell carcinoma (OSCC). Lymph node metastasis (LNM) significant adverse prognostic factor OSCC; however, mechanism LNM OSCC remains unclear, while strategies for managing cervical lymph nodes (CLNs) continue to evolve. At present, dissection necessary vast majority patients, but complications surgery can significantly impair patients’ postoperative quality life. A recent clinical trial discovery indicates that immunotherapy activate anti‐tumour T cells nearby nodes, leading vibrant discussions among clinicians about importance preserving during surgical treatment. Aim This review aims provide an overview where we are: current knowledge patterns management strategies, are going: prospects basic research on issue era immunotherapy. Result We summarize general LNM. The process encompasses four stages: Preparation, Unleash, Migration, Planting (‘PUMP’ principle). propose adopting ‘PRECISE’ model, overall workflow includes seven elements—prevention, radiology, preoperative evaluation, chemotherapy, immunotherapy, surgery, evaluation—for OSCC, promoting personalized precision medicine augmented by neoadjuvant therapy. further discussed advances provided outlook future directions. Conclusion Over past two centuries, our understanding have evolved, seeking more precise approaches reduce patient burden enhance survival Further should explore nodes’ role interactions, better, less invasive treatments improved outcomes.

Язык: Английский

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Less is more: Exploring neoadjuvant immunotherapy as a de-escalation strategy in head and neck squamous cell carcinoma treatment

Cancer Letters, Год журнала: 2024, Номер 598, С. 217095 - 217095

Опубликована: Июль 2, 2024

Язык: Английский

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A Review of Immunotherapy for Head and Neck Cancer

Journal of Dental Research, Год журнала: 2024, Номер 103(12), С. 1185 - 1196

Опубликована: Окт. 6, 2024

The introduction of immune checkpoint inhibitors (ICIs) to oncological care has transformed the management various malignancies, including head and neck squamous cell carcinoma (HNSCC), offering improved outcomes. first-line treatment recurrent malignant HNSCC for many years was combined platinum, 5-fluorouracil, cetuximab. Recently, ICI pembrolizumab approved as a treatment, with or without chemotherapy, based on tumor percentage programmed-death ligand 1 (PD-L1). Multiple (HN) cancer trials have subsequently explored immunotherapies in combination surgery, and/or radiation. Immunotherapy regimens may be personalized by biomarker, PD-L1 content, mutational burden, microsatellite instability. However, further clinical are needed refine biomarker-driven protocols standardize pathological methods guide regimen timing, sequencing, deescalation. Gaps remain using immunotherapy reverse oral premalignant lesions, particularly high-risk leukoplakias. A phase II nonrandomized controlled trial, nivolumab, showed 2-y cancer-free survival 73%, although larger needed. Guidelines also role dental evaluation before, during, after immunotherapy, specifically regard immune-related adverse events their impact recurrence. Standardized diagnostic coordination strategies close these gaps ensure continued success HN immunotherapy.

Язык: Английский

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Current Progress and Future Directions of Immunotherapy in Head and Neck Squamous Cell Carcinoma

JAMA Otolaryngology–Head & Neck Surgery, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

For decades, the 3 therapeutic pillars for head and neck squamous cell carcinoma (HNSCC) have been radiation therapy, chemotherapy, surgery. In recent years, a fourth pillar, immunotherapy, has shifted existing paradigm of oncologic care by improving survival outcomes. This narrative review highlights key completed ongoing clinical trials that led to new approaches are aiming further alter current standard care. Immunotherapy in HNSCC first saw success phase with immune checkpoint inhibitors (ICIs) programmed death 1 protein patients recurrent or metastatic (R/M) disease. However, only approximately 15% 20% R/M achieve durable responses. Subsequent aimed broaden ICIs definitive curative setting, combination established chemoradiation modalities. These studies yielded disappointing results, raising concerns concurrent administration ICI chemoradiation- radiation-induced attenuation responses may contribute lack efficacy. Therefore, attempted introduce sequentially, either prior surgery neoadjuvant setting following treatment adjuvant maintenance setting. demonstrated mixed results but promising initial from early demonstrating signals response. Further currently underway various combinatorial settings assess response rates survival. The introduction brought dramatic shift landscape HNSCC. Completed provided hope patients, failures several suggest based on biologic understanding required expand immunotherapeutic approaches.

Язык: Английский

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The role of T-cells in head and neck squamous cell carcinoma: From immunity to immunotherapy

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Окт. 20, 2022

Head and neck squamous cell carcinoma (HNSCC) encompass a group of complex entities tumours affecting the aerodigestive upper tract. The main risk factors are strongly related to tobacco alcohol consumption, but also HPV infection is often associated. Surgery, radiotherapy and/or chemotherapy standard treatments, though 5-year overall survival less than 50%. advances in genomics, molecular medicine, immunology, nanotechnology have shed light on tumour biology which helps clinical researchers obtain more efficacious toxic therapies. possess different immune escape mechanisms including diminishing response through modulating checkpoints, addition recruitment differentiation suppressive cells. insights into HNSCC its strong interaction with microenvironment highlights role immunomodulating agents. Recently, knowledge immunological features these has paved way for discovery effective biomarkers that allow better selection patients odds improving immunotherapy. Specially regarding checkpoint inhibitors antibodies, such as anti-PD-1/PD-L1 anti-CTLA-4 combination therapy or monotherapy. New immunotherapies treat head cancer carcinomas, CAR T cells nanoparticles been center attention this review, we discuss necessity finding targets generate cells, relevance evaluating specificity safety those

Язык: Английский

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Introducing Checkpoint Inhibitors Into the Curative Setting of Head and Neck Cancers: Lessons Learned, Future Considerations

American Society of Clinical Oncology Educational Book, Год журнала: 2022, Номер 42, С. 511 - 526

Опубликована: Май 6, 2022

The emergence of immunotherapy, in the form immune checkpoint inhibitors, has irrevocably altered paradigm cancer treatment over past decade. Multiple characteristics landscape head and neck squamous cell carcinoma suggest a strong rationale for use immunotherapies this disease. Data from studies with both single-agent chemotherapy immunotherapy combinations patients incurable, relapsed disease have confirmed potential inhibitors to be translated into settings which are treated curative intent. Indeed, number single-arm randomized studies, including trials surgery, chemotherapy, or radiotherapy, already been completed ongoing. In review, we present promising data used conjunction curative-intent as neoadjuvant/induction an adjuvant approach. addition, discuss fact that inhibitor therapy is, once again, allowing oncologists revisit role neoadjuvant part definitive regimens locally advanced carcinoma. Finally, address increasing interest exploiting synergistic interactions between radiotherapy context radical chemoradiotherapy regimens. As consequence these new areas research, optimistic next decade may see embedded within recommended standard-of-care

Язык: Английский

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High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(7), С. 3483 - 3483

Опубликована: Март 23, 2022

Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly heterogeneous group of tumors characterized by an incidence 650,000 new cases 350,000 deaths per year worldwide male to female ratio 3:1. The main risk factors are alcohol tobacco consumption Human Papillomavirus (HPV) infections. HNSCC divided into two subgroups, the HPV-negative (HPV−) HPV-positive (HPV+) which have different clinicopathological molecular profiles. However, patients still treated with same therapeutic regimens. It thus utmost importance characterize mechanisms underlying these differences find biomarkers novel targets towards personalized therapies. Epigenetic alterations hallmark cancer can be exploited as both promising potential targets. E6 E7 HPV oncoviral proteins besides targeting p53 pRb, impair expression activity several epigenetic regulators. While in DNA methylation patterns been well described HPV+ HPV− HNSCC, accurate histone post-translational modifications (hPTMs) characterization missing. Herein, we aim provide updated overview on impact hPTMs landscape HNSCC. Moreover, will also discuss sex gender bias how machinery could involved this process, taking account and/or field.

Язык: Английский

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EGFR pathway targeting drugs in head and neck cancer in the era of immunotherapy

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2022, Номер 1878(1), С. 188827 - 188827

Опубликована: Окт. 27, 2022

Язык: Английский

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Integrating Immunotherapy into Multimodal Treatment of Head and Neck Cancer

Cancers, Год журнала: 2023, Номер 15(3), С. 672 - 672

Опубликована: Янв. 21, 2023

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) have a poor prognosis, significant risk of progression or death despite multimodal treatment surgery, chemotherapy, radiotherapy. Immune checkpoint inhibitors targeting the programmed receptor-1 (PD1) dramatically changed landscape for recurrent/metastatic disease, improving overall survival in both first- second-line palliative settings. This success has driven investigation strategies incorporating immunotherapy earlier into curative-intent salvage HNSCC. review encompassed following three subjects, focus on recently reported ongoing clinical trials: (1) use neoadjuvant prior to surgery HNSCC, (2) immunochemoradiotherapy cancers, (3) novel uses HNSCC via combined modality, including reirradiation paradigms. The results these studies are eagerly awaited improve patient outcomes this challenging disease.

Язык: Английский

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