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

Cellular and Molecular Immunology, Год журнала: 2020, Номер 17(8), С. 807 - 821

Опубликована: Июль 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.

Язык: Английский

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Tertiary lymphoid structures improve immunotherapy and survival in melanoma

Nature, Год журнала: 2020, Номер 577(7791), С. 561 - 565

Опубликована: Янв. 15, 2020

Язык: Английский

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B cells are associated with survival and immunotherapy response in sarcoma

Nature, Год журнала: 2020, Номер 577(7791), С. 556 - 560

Опубликована: Янв. 15, 2020

Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes1,2. The clinical presentation patients different subtypes is often atypical, and responses to therapies such as immune checkpoint blockade vary widely3,4. To explain this variability, here we study gene expression profiles in 608 tumours across soft-tissue sarcoma. We establish an immune-based classification on the basis composition tumour microenvironment identify five distinct phenotypes: immune-low (A B), immune-high (D E), highly vascularized (C) groups. In situ analysis independent validation cohort shows that class E was characterized by presence tertiary lymphoid structures contain T cells follicular dendritic are particularly rich B cells. strongest prognostic factor even context high or low CD8+ cytotoxic contents. class-E demonstrated improved survival response rate PD1 pembrolizumab phase 2 trial. Together, work confirms sarcoma, unravels potential B-cell-rich guide decision-making treatments, which could have broader applications other diseases. Immune profiling sarcoma identifies levels B-cell infiltration therapy.

Язык: Английский

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The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy

Nature reviews. Cancer, Год журнала: 2020, Номер 20(11), С. 662 - 680

Опубликована: Авг. 4, 2020

Язык: Английский

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Hallmarks of response, resistance, and toxicity to immune checkpoint blockade

Cell, Год журнала: 2021, Номер 184(21), С. 5309 - 5337

Опубликована: Окт. 1, 2021

Язык: Английский

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Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers

Cell, Год журнала: 2020, Номер 182(4), С. 1044 - 1061.e18

Опубликована: Авг. 1, 2020

Язык: Английский

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Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front

Cell, Год журнала: 2020, Номер 182(5), С. 1341 - 1359.e19

Опубликована: Авг. 6, 2020

Antitumoral immunity requires organized, spatially nuanced interactions between components of the immune tumor microenvironment (iTME). Understanding this coordinated behavior in effective versus ineffective control will advance immunotherapies. We re-engineered co-detection by indexing (CODEX) for paraffin-embedded tissue microarrays, enabling simultaneous profiling 140 regions from 35 advanced-stage colorectal cancer (CRC) patients with 56 protein markers. identified nine conserved, distinct cellular neighborhoods (CNs)—a collection characteristic CRC iTME. Enrichment PD-1+CD4+ T cells only within a granulocyte CN positively correlated survival high-risk patient subset. Coupling and CNs, fragmentation cell macrophage disruption inter-CN communication was associated inferior outcomes. This study provides framework interrogating how complex biological processes, such as antitumoral immunity, occur through concerted actions spatial domains.

Язык: Английский

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Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition

Cell, Год журнала: 2021, Номер 184(3), С. 596 - 614.e14

Опубликована: Янв. 27, 2021

Checkpoint inhibitors (CPIs) augment adaptive immunity. Systematic pan-tumor analyses may reveal the relative importance of tumor-cell-intrinsic and microenvironmental features underpinning CPI sensitization. Here, we collated whole-exome transcriptomic data for >1,000 CPI-treated patients across seven tumor types, utilizing standardized bioinformatics workflows clinical outcome criteria to validate multivariable predictors Clonal mutation burden (TMB) was strongest predictor response, followed by total TMB CXCL9 expression. Subclonal TMB, somatic copy alteration burden, histocompatibility leukocyte antigen (HLA) evolutionary divergence failed attain pan-cancer significance. Dinucleotide variants were identified as a source immunogenic epitopes associated with radical amino acid substitutions enhanced peptide hydrophobicity/immunogenicity. Copy-number analysis revealed two additional determinants supported prior functional evidence: 9q34 (TRAF2) loss response CCND1 amplification resistance. Finally, single-cell RNA sequencing (RNA-seq) clonal neoantigen-reactive CD8 tumor-infiltrating lymphocytes (TILs), combined bulk RNA-seq CPI-responding tumors, CCR5 CXCL13 T-cell-intrinsic markers sensitivity.

Язык: Английский

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CD8+ T cell differentiation and dysfunction in cancer

Nature reviews. Immunology, Год журнала: 2021, Номер 22(4), С. 209 - 223

Опубликована: Июль 12, 2021

Язык: Английский

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Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics

Nature Reviews Genetics, Год журнала: 2021, Номер 22(10), С. 627 - 644

Опубликована: Июнь 18, 2021

Язык: Английский

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