Current Progress and Future Directions of Immunotherapy in Head and Neck Squamous Cell Carcinoma DOI
Edward S. Sim, Hoang C.B. Nguyen, Glenn J. Hanna

et al.

JAMA Otolaryngology–Head & Neck Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: Английский

The hallmarks of cancer immune evasion DOI
Claudia Galassi, Timothy A. Chan, Ilio Vitale

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(11), P. 1825 - 1863

Published: Oct. 10, 2024

Language: Английский

Citations

70
Single-cell sequencing to multi-omics: technologies and applications DOI Creative Commons
Xiangyu Wu, Xin Yang,

Yunhan Dai

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Sept. 27, 2024

Abstract Cells, as the fundamental units of life, contain multidimensional spatiotemporal information. Single-cell RNA sequencing (scRNA-seq) is revolutionizing biomedical science by analyzing cellular state and intercellular heterogeneity. Undoubtedly, single-cell transcriptomics has emerged one most vibrant research fields today. With optimization innovation technologies, intricate details concealed within cells are gradually unveiled. The combination scRNA-seq other multi-omics at forefront field. This involves simultaneously measuring various omics data individual cells, expanding our understanding across a broader spectrum dimensions. precisely captures aspects transcriptomes, immune repertoire, spatial information, temporal epitopes, in diverse contexts. In addition to depicting cell atlas normal or diseased tissues, it also provides cornerstone for studying differentiation development patterns, disease heterogeneity, drug resistance mechanisms, treatment strategies. Herein, we review traditional technologies outline latest advancements multi-omics. We summarize current status challenges applying biological clinical applications. Finally, discuss limitations potential strategies address them.

Language: Английский

Citations

21
Integrative molecular and spatial analysis reveals evolutionary dynamics and tumor-immune interplay of in situ and invasive acral melanoma DOI Creative Commons
Hengkang Liu, Jiawen Gao,

Mei Feng

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(6), P. 1067 - 1085.e11

Published: May 16, 2024

In acral melanoma (AM), progression from in situ (AMis) to invasive AM (iAM) leads significantly reduced survival. However, evolutionary dynamics during this process remain elusive. Here, we report integrative molecular and spatial characterization of 147 AMs using genomics, bulk single-cell transcriptomics, transcriptomics proteomics. Vertical invasion AMis iAM displays an early monoclonal seeding pattern. The subsequent regional expansion exhibits two distinct patterns, clonal subclonal diversification. Notably, subtyping reveals aggressive subset featured with diversification, increased epithelial-mesenchymal transition (EMT), enrichment APOE

Language: Английский

Citations

19
Integrated cancer cell-specific single-cell RNA-seq datasets of immune checkpoint blockade-treated patients DOI Creative Commons
Mahnoor Gondal, Marcin Cieślik, Arul M. Chinnaiyan

et al.

Scientific Data, Journal Year: 2025, Volume and Issue: 12(1)

Published: Jan. 22, 2025

Abstract Immune checkpoint blockade (ICB) therapies have emerged as a promising avenue for the treatment of various cancers. Despite their success, efficacy these treatments is variable across patients and cancer types. Numerous single-cell RNA-sequencing (scRNA-seq) studies been conducted to unravel cell-specific responses ICB treatment. However, are limited in sample sizes require advanced coding skills exploration. Here, we compiled eight scRNA-seq datasets from nine types, encompassing 223 patients, 90,270 cells, 265,671 other cell This compilation forms unique resource tailored investigate how cells respond We meticulously curated, quality-checked, pre-processed, analyzed data, ensuring easy access researchers. Moreover, designed user-friendly interface seamless By sharing code data creating interfaces, aim assist fellow These resources offer valuable support those interested leveraging exploring diverse facilitating comprehensive understanding responses.

Language: Английский

Citations

2
Cancer cell states: Lessons from ten years of single-cell RNA-sequencing of human tumors DOI
Itay Tirosh, Mario L. Suvà

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(9), P. 1497 - 1506

Published: Aug. 29, 2024

Language: Английский

Citations

15
Immunotherapy in melanoma: Can we predict response to treatment with circulating biomarkers? DOI Creative Commons
Elena Splendiani, Zein Mersini Besharat, Alessia Covre

et al.

Pharmacology & Therapeutics, Journal Year: 2024, Volume and Issue: 256, P. 108613 - 108613

Published: Feb. 16, 2024

Melanoma is the most aggressive form of skin cancer, representing approximately 4% all cutaneous neoplasms it accounts for up to 80% deaths. Advanced stages melanoma involve metastatic processes and are associated with high mortality morbidity, mainly due rapid dissemination heterogeneous responses current therapies including immunotherapy. Indeed, immune checkpoints inhibitors (ICIs), either alone or in combination other currently used (MM) linked an increase patient survival. Of note, number therapeutic regimens MM patients using ICIs has increased, highlighting a growing need reliable biomarkers that can both predict monitor response ICIs. In this context, circulating biomarkers, such as DNA, RNA, proteins, cells, have emerged their ability detect disease status. Moreover, blood tests minimally invasive provide attractive option avoiding stressful medical procedures. This systematic review summarizes evaluate possibility non-invasive biomarker signature guide decisions. The studies reported here offer valuable insight into how role personalized treatments receiving therapy, emphasizing rigorous clinical trials confirm findings establish standardized

Language: Английский

Citations

14
Cancer drug-tolerant persister cells: from biological questions to clinical opportunities DOI
Mariangela Russo,

Mengnuo Chen,

Elisa Mariella

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(10), P. 694 - 717

Published: Sept. 2, 2024

Language: Английский

Citations

14
Immune escape and metastasis mechanisms in melanoma: breaking down the dichotomy DOI Creative Commons

Carl A. Shirley,

Gagan Chhabra,

Deeba Amiri

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 14, 2024

Melanoma is one of the most lethal neoplasms skin. Despite revolutionary introduction immune checkpoint inhibitors, metastatic spread, and recurrence remain critical problems in resistant cases. employs a multitude mechanisms to subvert system successfully metastasize distant organs. Concerningly, recent research also shows that tumor cells can disseminate early during melanoma progression enter dormant states, eventually leading metastases at future time. Immune escape metastasis have previously been viewed as separate phenomena; however, accumulating evidence breaking down this dichotomy. Recent into progressive provides dedifferentiation similar classical epithelial mesenchymal transition (EMT), genes involved neural crest stem cell maintenance, hypoxia/acidosis, are important factors simultaneously metastasis. The likeness between EMT dissemination, differences, become apparent these contexts. Detailed knowledge behind “dual drivers” promoting metastatically inclined immunosuppressive environments yield novel strategies effective disabling multiple facets progression. Furthermore, understanding through drivers may provide insight towards treatments capable preventing arising from dissemination or improving immunotherapy outcomes.

Language: Английский

Citations

13
Intratumoral Collagen Deposition Supports Angiogenesis Suggesting Anti‐angiogenic Therapy in Armored and Cold Tumors DOI Creative Commons
Jie Mei, Kai Yang,

Xinkang Zhang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Abstract A previous study classifies solid tumors based on collagen deposition and immune infiltration abundance, identifying a refractory subtype termed armored & cold tumors, characterized by elevated diminished infiltration. Beyond its impact infiltration, also influences tumor angiogenesis. This systematically analyzes the association between immuno‐collagenic subtypes angiogenesis across diverse cancer types. As result, exhibit highest angiogenic activity in lung adenocarcinoma (LUAD). Single‐cell spatial transcriptomics reveal close interactions co‐localization of fibroblasts endothelial cells. In vitro experiments demonstrate that stimulates cells to express vascular growth factor (VEGFA) directly enhances vessel formation cell proliferation through sex determining region Y box 18 (SOX18) upregulation. Collagen inhibition via multiple approaches effectively suppresses vivo. addition, display superior responsiveness anti‐angiogenic therapy advanced LUAD cohorts. Post‐immunotherapy resistance, transformation into emerges as potential biomarker for selecting therapy. summary, is shown drive various cancers, providing novel actionable framework refine therapeutic strategies combining chemotherapy with treatments.

Language: Английский

Citations

1
ZEB1 controls a lineage-specific transcriptional program essential for melanoma cell state transitions DOI Creative Commons
Simon Durand,

Yaqi Tang,

Roxane M. Pommier

et al.

Oncogene, Journal Year: 2024, Volume and Issue: 43(20), P. 1489 - 1505

Published: March 22, 2024

Abstract Cell plasticity sustains intra-tumor heterogeneity and treatment resistance in melanoma. Deciphering the transcriptional mechanisms governing reversible phenotypic transitions between proliferative/differentiated invasive/stem-like states is required. Expression of ZEB1 transcription factor frequently activated melanoma, where it fosters adaptive to targeted therapies. Here, we performed a genome-wide characterization targets, by combining ChIP-sequencing RNA-sequencing, upon phenotype switching melanoma models. We identified validated binding peaks promoter key lineage-specific genes crucial for cell identity. Mechanistically, negatively regulates SOX10-MITF dependent proliferative/melanocytic programs positively AP-1 driven invasive stem-like programs. Comparative analyses with breast carcinoma cells revealed binding, leading design more reliable melanoma-specific regulon. then developed single-cell spatial multiplexed characterize intra-tumoral human samples. Combined scRNA-Seq analyses, our findings confirmed increased expression Neural-Crest-like mesenchymal cells, underscoring its significance vivo both populations. Overall, results define as major regulator provide better understanding sustaining

Language: Английский

Citations

7