Interactions of Indoleamine 2,3‐dioxygenase‐expressing LAMP3+ dendritic cells with CD4+ regulatory T cells and CD8+ exhausted T cells: synergistically remodeling of the immunosuppressive microenvironment in cervical cancer and therapeutic implications DOI Creative Commons
Xinyu Qu, Yumeng Wang, Qian Jiang

et al.

Cancer Communications, Journal Year: 2023, Volume and Issue: 43(11), P. 1207 - 1228

Published: Oct. 4, 2023

Abstract Background Cervical cancer (CC) is the fourth most common in women worldwide. Although immunotherapy has been applied clinical practice, its therapeutic efficacy remains far from satisfactory, necessitating further investigation of mechanism CC immune remodeling and exploration novel treatment targets. This study aimed to investigate explore potential Methods We conducted single‐cell RNA sequencing on a total 17 specimens, including normal cervical tissues, high‐grade squamous intraepithelial lesions, tissues. To validate our findings, we multicolor immunohistochemical staining tissues constructed subcutaneous tumorigenesis model C57BL/6 mice using murine cell lines (TC1) evaluate effectiveness combination therapy involving indoleamine 2,3‐dioxygenase 1 (IDO1) inhibition checkpoint blockade (ICB). used unpaired two‐tailed Student's t‐test, Mann‐Whitney test, or Kruskal‐Wallis test compare continuous data between two groups one‐way ANOVA with Tukey's post hoc multiple groups. Results Malignant epithelial cells did not manifest noticeable signs tumor escape, whereas lysosomal‐associated membrane protein 3‐positive (LAMP3 + ) dendritic (DCs) mature state immunoregulatory roles were found express IDO1 affect tryptophan metabolism. These interacted both tumor‐reactive exhausted CD8 T CD4 regulatory cells, synergistically forming vicious immunosuppressive cycle mediating escape. Further validation through showed co‐localization neoantigen‐reactive (CD3 , /CD8 PD‐1 LAMP3 DCs (CD80 PD‐L1 ). Additionally, inhibitor an ICB agent significantly reduced volume mouse compared alone. Conclusions Our suggested that consisting targeting could improve current immunotherapies. results provided crucial insights for designing drugs conducting future trials CC.

Language: Английский

Tumor heterogeneity reshapes the tumor microenvironment to influence drug resistance DOI Creative Commons
Aiping Zhang, Kai Miao, Heng Sun

et al.

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(7), P. 3019 - 3033

Published: Jan. 1, 2022

Tumor heterogeneity is one of the hallmarks cancer and a challenge in field oncology.Tumor main cause drug resistance, leading to therapeutic failure.Mechanically, tumor either directly affects targets or shapes microenvironment (TME) by defining transcriptomic phenotypic profiles influence resistance.Tumor evolves spatially temporally during development, constant reprogramming TME.Advances molecular profiling technologies precision oncology platforms have allowed us uncover impact on resistance context TME.In this review, we focus processes which genomic mutations drive mechanisms through reprograms TME affect patient prognosis.

Language: Английский

Citations

151
Refining colorectal cancer classification and clinical stratification through a single-cell atlas DOI Creative Commons
Ateeq Khaliq, Cihat Erdoğan, Zeyneb Kurt

et al.

Genome biology, Journal Year: 2022, Volume and Issue: 23(1)

Published: May 10, 2022

Colorectal cancer (CRC) consensus molecular subtypes (CMS) have different immunological, stromal cell, and clinicopathological characteristics. Single-cell characterization of CMS subtype tumor microenvironments is required to elucidate mechanisms stroma cell contributions pathogenesis which may advance subtype-specific therapeutic development. We interrogate racially diverse human CRC samples analyze multiple independent external cohorts for a total 487,829 single cells enabling high-resolution depiction the cellular diversity heterogeneity within microenvironmental cells.Tumor recapitulate individual subgroups yet exhibit significant intratumoral heterogeneity. Both CMS1 microsatellite instability (MSI-H) CRCs stable (MSS) demonstrate similar pathway activations at epithelial level. However, CD8+ cytotoxic T phenotype infiltration in MSI-H explain why these tumors respond immune checkpoint inhibitors. Cellular transcriptomic profiles exist continuum contrast discrete proposed by studies utilizing bulk transcriptomics. note dichotomy across exists patients with high cancer-associated fibroblasts (CAFs) C1Q+TAM content poor outcomes, providing higher level personalization precision than would distinct subtypes. Additionally, we discover CAF known be associated immunotherapy resistance.Distinct CAFs C1Q+ TAMs are sufficient predictive ability simpler signature based on phenotypes could stratify patient prognosis greater precision. Therapeutically targeting specific C1Q + promote responses patients.

Language: Английский

Citations

121
Unveiling the mechanisms and challenges of cancer drug resistance DOI Creative Commons
Sameer Ullah Khan, Kaneez Fatima,

Shariqa Aisha

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 12, 2024

Abstract Cancer treatment faces many hurdles and resistance is one among them. Anti-cancer strategies are evolving due to innate acquired capacity, governed by genetic, epigenetic, proteomic, metabolic, or microenvironmental cues that ultimately enable selected cancer cells survive progress under unfavorable conditions. Although the mechanism of drug being widely studied generate new target-based drugs with better potency than existing ones. However, broader flexibility in resistance, advanced therapeutic options efficacy need be explored. Combination therapy an alternative a success rate though risk amplified side effects commonplace. Moreover, recent groundbreaking precision immune ways overcome has revolutionized anticancer greater extent only limitation individual-specific needs further attention. This review will focus on challenges opted withstand current therapies at molecular level also highlights emerging -like immunological, stem cell-based may prove have potential challenge problem resistance.

Language: Английский

Citations

101
Biomarkers for immunotherapy of hepatocellular carcinoma DOI
Tim F. Greten, Augusto Villanueva, Firouzeh Korangy

et al.

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(11), P. 780 - 798

Published: Sept. 19, 2023

Language: Английский

Citations

97
Targeting tumor-associated macrophages in hepatocellular carcinoma: biology, strategy, and immunotherapy DOI Creative Commons
Hongyu Zheng, Xueqiang Peng, Shuo Yang

et al.

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Feb. 15, 2023

Abstract Hepatocellular carcinoma (HCC), one of the most malignant tumors, is characterized by its stubborn immunosuppressive microenvironment. As main members tumor microenvironment (TME) HCC, tumor-associated macrophages (TAMs) play a critical role in occurrence and development, including stimulating angiogenesis, enhancing immunosuppression, promoting drug resistance cancer metastasis. This review describes origin as well phenotypic heterogeneity TAMs their potential effects on development HCC also discusses about various adjuvant therapy based strategies that can be used for targeting TAMs. In addition, we have highlighted different treatment modalities immunotherapy, small molecular inhibitors, immune checkpoint antibodies, vaccines, adoptive cellular nanocarriers delivery, to explore novel combination therapies provide feasible therapeutic options clinically improving prognosis quality life patients.

Language: Английский

Citations

58
Tracking tumor heterogeneity and progression with near‐infrared II fluorophores DOI Creative Commons
Xin Qi, Huizhen Ma, Hao Wang

et al.

Exploration, Journal Year: 2023, Volume and Issue: 3(2)

Published: March 16, 2023

Abstract Heterogeneous cells are the main feature of tumors with unique genetic and phenotypic characteristics, which can stimulate differentially progression, metastasis, drug resistance. Importantly, heterogeneity is pervasive in human malignant tumors, identification degree tumor individual progression a critical task for treatment. However, current medical tests cannot meet these needs; particular, need noninvasive visualization single‐cell heterogeneity. Near‐infrared II (NIR‐II, 1000–1700 nm) imaging exhibits an exciting prospect non‐invasive monitoring due to high temporal‐spatial resolution. More importantly, NIR‐II displays more extended tissue penetration depths reduced backgrounds because significantly lower photon scattering autofluorescence than traditional near‐infrared I (NIR‐I) imaging. In this review, we summarize systematically advances made imaging, especially detection as well As visual inspection modality, shows promising prospects understanding differences envisioned have potential be used clinically.

Language: Английский

Citations

58
Prognostic signatures of sphingolipids: Understanding the immune landscape and predictive role in immunotherapy response and outcomes of hepatocellular carcinoma DOI Creative Commons
Xin Zhang, Jinke Zhuge, Jinhui Liu

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 17, 2023

Hepatocellular carcinoma (HCC) is a complex disease with poor outlook for patients in advanced stages. Immune cells play an important role the progression of HCC. The metabolism sphingolipids functions both tumor growth and immune infiltration. However, little research has focused on using sphingolipid factors to predict HCC prognosis. This study aimed identify key genes (SPGs) develop reliable prognostic model based these genes.The TCGA, GEO, ICGC datasets were grouped SPGs obtained from InnateDB portal. A gene signature was created by applying LASSO-Cox analysis evaluating it Cox regression. validity verified GEO datasets. microenvironment (TME) examined ESTIMATE CIBERSORT, potential therapeutic targets identified through machine learning. Single-cell sequencing used examine distribution within TME. Cell viability migration tested confirm SPGs.We 28 that have impact survival. Using clinicopathological features 6 genes, we developed nomogram high- low-risk groups found distinct characteristics response drugs. Unlike CD8 T cells, M0 M2 macrophages be highly infiltrated TME high-risk subgroup. High levels good indicator immunotherapy. In cell function experiments, SMPD2 CSTA enhance survival Huh7 while silencing increased sensitivity lapatinib.The presents six-gene can aid clinicians choosing personalized treatments patients. Furthermore, uncovers connection between sphingolipid-related microenvironment, offering novel approach By focusing crucial like CSTA, efficacy anti-tumor therapy cells.

Language: Английский

Citations

46
Intratumoural microbiome can predict the prognosis of hepatocellular carcinoma after surgery DOI Creative Commons
Lejia Sun, Xindi Ke,

Ai Guan

et al.

Clinical and Translational Medicine, Journal Year: 2023, Volume and Issue: 13(7)

Published: July 1, 2023

The dismal prognosis of hepatocellular carcinoma (HCC) is closely associated with characteristics the tumour microenvironment (TME). Recent studies have confirmed presence and potential influence microbiome in TME on cancer progression. Elucidating relationship between microbes could provide valuable insights into novel diagnostic markers therapeutic strategies for HCC thus warrants a closer investigation role intratumoural TME.

Language: Английский

Citations

43
Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives DOI Creative Commons

Ke-Yu Shen,

Ying Zhu,

Sun‐Zhe Xie

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: April 29, 2024

Abstract Hepatocellular carcinoma (HCC) is a major health concern worldwide, with limited therapeutic options and poor prognosis. In recent years, immunotherapies such as immune checkpoint inhibitors (ICIs) have made great progress in the systemic treatment of HCC. The combination treatments based on ICIs been trend this area. Recently, dual blockade durvalumab plus tremelimumab has also emerged an effective for advanced However, majority HCC patients obtain benefits. Understanding immunological rationale exploring novel ways to improve efficacy immunotherapy drawn much attention. review, we summarize latest area, ongoing clinical trials immune-based therapies, well strategies chimeric antigen receptor T cells, personalized neoantigen vaccines, oncolytic viruses, bispecific antibodies.

Language: Английский

Citations

41
Heterogeneity of hepatocellular carcinoma: from mechanisms to clinical implications DOI Creative Commons
Fatema Safri,

Romario Nguyen,

Shadi Zerehpooshnesfchi

et al.

Cancer Gene Therapy, Journal Year: 2024, Volume and Issue: 31(8), P. 1105 - 1112

Published: March 18, 2024

Abstract Hepatocellular Carcinoma (HCC) is one of the most common types primary liver cancer. Current treatment options have limited efficacy against this malignancy, primarily owing to difficulties in early detection and inherent resistance existing drugs. Tumor heterogeneity a pivotal factor contributing significantly recurrent manifestations HCC. Intratumoral an important aspect spectrum complex tumor contributes late diagnosis failure. Therefore, it crucial thoroughly understand molecular mechanisms how develops. This review aims summarize possible dimensions with emphasis on intratumoral heterogeneity, evaluate its profound impact therapeutic strategies for HCC, explore suitability appropriate pre-clinical models that can be used best study heterogeneity; thus, opening new avenues cancer treatment.

Language: Английский

Citations

29