Genomic and Immune Profiling of Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Therapy Versus Upfront Surgery Identifies Novel Immunogenic Cell Death‐Based Signatures for Predicting Clinical Outcomes DOI Creative Commons

Peidong Song,

Wenze Tian,

Yujia Zheng

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(4)

Published: April 1, 2025

It remains undetermined regarding the impact of neoadjuvant therapy on immunogenic cell death (ICD) and subsequent tumor microenvironment (TME) remodeling in esophageal squamous carcinoma (ESCC). And it is paramount significance to identify beneficiaries from treatment-naïve ESCC. In this study, 88 ESCC samples undergoing plus surgery (NA+S) or alone (SA) were subjected bulk-RNA sequencing. A five-gene RINscore incorporating ICD-related signature genes with TME-based hub was established predict clinical outcomes pharmacological responses, which SLAMF7 IL1R1 selected out as co-expressed genes. The regulatory mechanism repressive co-transcription factor BATF further demonstrated. Our data demonstrated that NA+S led high abundance kinds T helper cells, nature killer cells M1-like macrophages increased CD8+T infiltration compared SA. ICD phenotypes characterized determine their differences TME potential benefits NA. findings not only offered novel insights into distinct profiles different therapeutic modes, but also provided RINscore, may aid oncologists determining individualized (neo)adjuvant immunotherapy regimen.

Language: Английский

Spatiotemporal single-cell analysis decodes cellular dynamics underlying different responses to immunotherapy in colorectal cancer DOI Creative Commons
Yuqing Chen, Dongfang Wang, Yingjie Li

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(7), P. 1268 - 1285.e7

Published: July 1, 2024

Expanding the efficacy of immune checkpoint blockade (ICB) in colorectal cancer (CRC) presses for a comprehensive understanding treatment responsiveness. Here, we analyze multiple sequential single-cell samples from 22 patients undergoing PD-1 to map evolution local and systemic immunity CRC patients. In tumors, identify coordinated cellular programs exhibiting distinct response associations. Specifically, exhausted T (Tex) or tumor-reactive-like CD8+ (Ttr-like) cells are closely related efficacy, Tex show correlated proportion changes with other tumor-enriched cell types following blockade. addition, reveal less-exhausted phenotype blood-associated Ttr-like tumors find that their higher abundance suggests better outcomes. Finally, major histocompatibility complex (MHC) II-related signature circulating at baseline is linked superior responses. Our study provides insights into spatiotemporal dynamics neoadjuvant CRC.

Language: Английский

Citations

23
Biological and clinical significance of tumour-infiltrating lymphocytes in the era of immunotherapy: a multidimensional approach DOI
Miguel López de Rodas, María Villalba, Miguel F. Sanmamed

et al.

Nature Reviews Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Language: Английский

Citations

5
Combination anti-PD-1 and anti-CTLA-4 therapy generates waves of clonal responses that include progenitor-exhausted CD8+ T cells DOI
Kevin Wang,

Paulina Coutifaris,

David Brocks

et al.

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(9), P. 1582 - 1597.e10

Published: Aug. 29, 2024

Language: Английский

Citations

13
Unraveling the tumor microenvironment of esophageal squamous cell carcinoma through single-cell sequencing: A comprehensive review DOI

Lingyu Qi,

Jiaxin Wang, Shuang Hou

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189264 - 189264

Published: Jan. 1, 2025

Language: Английский

Citations

1
Emerging clinical applications of single-cell RNA sequencing in oncology DOI
Emily Boxer,

Nisan Feigin,

Roi Tschernichovsky

et al.

Nature Reviews Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Language: Английский

Citations

1
The single cell immunogenomic landscape after neoadjuvant immunotherapy combined chemotherapy in esophageal squamous cell carcinoma DOI
Zheyi Wang, Yue Zhao, Yang Wo

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 593, P. 216951 - 216951

Published: May 10, 2024

Language: Английский

Citations

8
Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer DOI
Xiaojun Zhang, Yan Yu, Heping Zhao

et al.

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(16), P. 2195 - 2208

Published: April 26, 2024

As a highly invasive malignancy, esophageal cancer (EC) is global health issue, and was the eighth most prevalent sixth leading cause of cancer-related death worldwide in 2020. Due to its immunogenic nature, emer-ging immunotherapy approaches, such as immune checkpoint blockade, have demonstrated promising efficacy treating EC; however, certain limitations challenges still exist. In addition, tumors may exhibit primary or acquired resistance tumor microenvironment (TIME); thus, understanding TIME urgent crucial, especially given im-portance an immunosuppressive progression. The aim this review better elucidate mechanisms suppressive TIME, including cell infiltration, subsets, cytokines signaling pathways EC patients, well downregulated expression major histocompatibility complex molecules cells, obtain differences patient responses immunotherapeutic strategies accurately predict immunotherapies. Therefore, personalized treatments could be developed maximize advantages immunotherapy.

Language: Английский

Citations

5
Revolutionizing tumor immunotherapy: unleashing the power of progenitor exhausted T cells DOI Creative Commons
Fang Zhang, Xinyi Ding, Hao Huang

et al.

Cancer Biology and Medicine, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 14

Published: May 31, 2024

In exploring persistent infections and malignancies, a distinctive subgroup of CD8+ T cells, progenitor exhausted (Tpex) has been identified. These Tpex cells are notable for their remarkable self-renewal rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that expand differentiate into responsive thus underscoring critical role the immunotherapeutic retort. Clinical examinations further clarified robust positive correlation between proportional abundance enhanced clinical prognosis. found noteworthy applications formulation inventive approaches against tumors. This review describes functions tumor milieu, particularly potential utility immunotherapy. Precisely directing may be essential to achieving successful outcomes

Language: Английский

Citations

5
A machine learning radiomics based on enhanced computed tomography to predict neoadjuvant immunotherapy for resectable esophageal squamous cell carcinoma DOI Creative Commons
Jialing Wang,

Liansha Tang,

Xia Zhong

et al.

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

Published: June 14, 2024

Background Patients with resectable esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant immunotherapy (NIT) display variable treatment responses. The purpose of this study is to establish and validate a radiomics based on enhanced computed tomography (CT) combined clinical data predict the major pathological response NIT in ESCC patients. Methods This retrospective included 82 patients who were randomly divided into training group (n = 57) validation 25). Radiomic features derived from tumor region CT images obtained before treatment. After feature reduction screening, was established. Logistic regression analysis conducted select variables. predictive model integrating constructed presented as nomogram. Area under curve (AUC) applied evaluate ability models, decision (DCA) calibration curves performed test application models. Results One (radiotherapy) 10 radiomic identified for model. integrated could achieve excellent performance, AUC values 0.93 (95% CI 0.87–0.99) 0.85 0.69–1.00) group, respectively. DCA demonstrated good feasibility utility Conclusion Enhanced image-based high accuracy robustness. developed offers valuable tool assessing efficacy prior initiating therapy, thus providing individualized regimens

Language: Английский

Citations

5
Cathepsin L promotes oesophageal squamous cell carcinoma development and may be associated with tumour-associated macrophages DOI Creative Commons

Zhenhu Zhang,

Jianyu Wang,

Yamin Shi

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e29273 - e29273

Published: April 1, 2024

BackgroundOesophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths worldwide because existing treatments are often insufficient. Therefore, new, reliable biomarkers must be identified. CTSL overexpression closely associated with tumour progression and poor prognosis. However, the role mechanism as an oncogene in ESCC remain unclear.MethodsGenome-wide association study (GWAS) data were used for Mendelian randomization analysis to investigate possible relationships between ESCC. The correlation expression prognosis was analysed using GEO, TCGA, GEPIA data. We compared among types single-cell sequencing. Correlations microenvironment, immune infiltration, mutational load, immunological checkpoints, treatment sensitivity patients investigated. Finally, mouse models cellular investigations, we assessed effects on growth, apoptosis, metastasis cells.ResultsCTSL overexpressed correlated also discovered its close immunity, especially tumour-associated macrophages checkpoints microenvironment. may play key development by affecting M2 macrophage polarisation. marker genes showed significant positive correlations. confirmed relationship our vitro vivo experiments demonstrated that promoted proliferation migration cells, validating bioinformatic analysis.ConclusionCTSL emerged crucial gene influences patient particularly macrophages. targeting or modulating levels provide new therapeutic strategies

Language: Английский

Citations

4