The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications

Cellular and Molecular Immunology, Journal Year: 2020, Volume and Issue: 17(8), P. 807 - 821

Published: July 1, 2020

Abstract Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology. Several types immunotherapy, including adoptive cell transfer (ACT) immune checkpoint inhibitors (ICIs), have obtained durable clinical responses, but their efficacies vary, only subsets patients can benefit from them. Immune infiltrates in microenvironment (TME) been shown to play a key role development will affect outcomes patients. Comprehensive profiling tumor-infiltrating cells would shed light on mechanisms cancer–immune evasion, thus providing opportunities for novel therapeutic strategies. However, highly heterogeneous dynamic nature TME impedes precise dissection intratumoral cells. With recent advances single-cell technologies such as RNA sequencing (scRNA-seq) mass cytometry, systematic interrogation is feasible provide insights into functional diversities In this review, we outline progress particularly by focusing landmark studies characterization tumor-associated cells, summarize phenotypic connections with immunotherapy. We believe review could strengthen our understanding facilitate elucidation modulation progression, guide immunotherapies treatment.

Language: Английский

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Intratumoral heterogeneity in cancer progression and response to immunotherapy

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(2), P. 212 - 224

Published: Feb. 1, 2021

Language: Английский

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Global Epidemiology and Genetics of Hepatocellular Carcinoma

Gastroenterology, Journal Year: 2023, Volume and Issue: 164(5), P. 766 - 782

Published: Feb. 2, 2023

Language: Английский

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Molecular pathogenesis and systemic therapies for hepatocellular carcinoma

Nature Cancer, Journal Year: 2022, Volume and Issue: 3(4), P. 386 - 401

Published: April 28, 2022

Language: Английский

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Single‐cell RNA sequencing in cancer research

Journal of Experimental & Clinical Cancer Research, Journal Year: 2021, Volume and Issue: 40(1)

Published: March 1, 2021

Abstract Single-cell RNA sequencing (scRNA-seq), a technology that analyzes transcriptomes of complex tissues at single-cell levels, can identify differential gene expression and epigenetic factors caused by mutations in unicellular genomes, as well new cell-specific markers cell types. scRNA-seq plays an important role various aspects tumor research. It reveals the heterogeneity cells monitors progress development, thereby preventing further cellular deterioration. Furthermore, transcriptome analysis immune tissue be used to classify cells, their escape mechanisms drug resistance mechanisms, develop effective clinical targeted therapies combined with immunotherapy. Moreover, this method enables study intercellular communication interaction non-malignant reveal carcinogenesis. provides technical means for development research is expected make significant breakthroughs field. This review focuses on principles scRNA-seq, emphasis application heterogeneity, pathogenesis, treatment.

Language: Английский

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Comprehensive analysis of spatial architecture in primary liver cancer

Science Advances, Journal Year: 2021, Volume and Issue: 7(51)

Published: Dec. 17, 2021

Spatial transcriptome technique was applied to decipher the spatial architecture and TME characteristics of liver cancers.

Language: Английский

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Single-cell RNA sequencing shows the immunosuppressive landscape and tumor heterogeneity of HBV-associated hepatocellular carcinoma

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: June 17, 2021

Abstract Interaction between tumor cells and immune in the microenvironment is important cancer development. Immune interact with to shape this process. Here, we use single-cell RNA sequencing analysis delineate landscape heterogeneity a cohort of patients HBV-associated human hepatocellular carcinoma (HCC). We found that tumor-associated macrophages suppress T cell infiltration TIGIT-NECTIN2 interaction regulates immunosuppressive environment. The state transition towards more exhaustive status exemplifies overall cancer-promoting immunocellular landscape. Furthermore, global molecular profiles reveals co-existence intra-tumoral inter-tumoral heterogeneity, but apparent latter. This intercellular interactions provides mechanistic information for design efficacious immune-oncology treatments carcinoma.

Language: Английский

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AlphaFold accelerates artificial intelligence powered drug discovery: efficient discovery of a novel CDK20 small molecule inhibitor

Chemical Science, Journal Year: 2023, Volume and Issue: 14(6), P. 1443 - 1452

Published: Jan. 1, 2023

The application of artificial intelligence (AI) has been considered a revolutionary change in drug discovery and development. In 2020, the AlphaFold computer program predicted protein structures for whole human genome, which remarkable breakthrough both AI applications structural biology. Despite varying confidence levels, these could still significantly contribute to structure-based design novel targets, especially ones with no or limited information. this work, we successfully applied our end-to-end AI-powered engines, including biocomputational platform PandaOmics generative chemistry Chemistry42. A hit molecule against target without an experimental structure was identified, starting from selection towards identification, cost- time-efficient manner. provided interest treatment hepatocellular carcinoma (HCC) Chemistry42 generated molecules based on by AlphaFold, selected were synthesized tested biological assays. Through approach, identified small compound cyclin-dependent kinase 20 (CDK20) binding constant Kd value 9.2 ± 0.5 μM (n = 3) within 30 days after only synthesizing 7 compounds. Based available data, second round generation conducted through this, more potent molecule, ISM042-2-048, discovered average 566.7 256.2 nM 3). Compound ISM042-2-048 also showed good CDK20 inhibitory activity IC50 33.4 22.6 addition, demonstrated selective anti-proliferation HCC cell line overexpression, Huh7, 208.7 3.3 nM, compared counter screen HEK293 (IC50 1706.7 670.0 nM). This work is first demonstration applying identification process discovery.

Language: Английский

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Functions and mechanisms of circular RNAs in cancer radiotherapy and chemotherapy resistance

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: March 14, 2020

Abstract Circular RNAs (circRNAs), one type of non-coding RNA, were initially misinterpreted as nonfunctional products pre-mRNA mis-splicing. Currently, circRNAs have been proven to manipulate the functions diverse molecules, including RNAs, mRNAs, DNAs and proteins, regulate cell activities in physiology pathology. Accumulating evidence indicates that play critical roles tumor genesis, development, sensitivity radiation chemotherapy. Radiotherapy chemotherapy are two primary types intervention for most cancers, but their therapeutic efficacies usually retarded by intrinsic acquired resistance. Thus, it is urgent develop new strategies improve responses. To achieve this, clarification underlying mechanisms affecting responses cancer needed. This review summarizes recent progress resistance chemotherapy, discusses limitations available knowledge potential future directions.

Language: Английский

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Inflamed and non-inflamed classes of HCC: a revised immunogenomic classification

Gut, Journal Year: 2022, Volume and Issue: 72(1), P. 129 - 140

Published: Feb. 23, 2022

We previously reported a characterisation of the hepatocellular carcinoma (HCC) immune contexture and described an immune-specific class. now aim to further delineate immunogenomic classification HCC incorporate features that explain responses/resistance immunotherapy.

Language: Английский

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