B cells and the coordination of immune checkpoint inhibitor response in patients with solid tumors DOI Creative Commons
Ronan Flippot, Marcus de Melo Teixeira,

Macarena Rey-Cárdenas

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(4), P. e008636 - e008636

Published: April 1, 2024

Immunotherapy profoundly changed the landscape of cancer therapy by providing long-lasting responses in subsets patients and is now standard care several solid tumor types. However, immunotherapy activity beyond conventional immune checkpoint inhibition plateauing, biomarkers are overall lacking to guide treatment selection. Most studies have focused on T cell engagement response, but there a growing evidence that B cells may be key players establishment an organized notably through tertiary lymphoid structures. Mechanisms response include antibody-dependent cellular cytotoxicity phagocytosis, promotion CD4+ CD8+ activation, maintenance antitumor memory. In types, higher levels cells, specific subpopulations, or presence structures been associated with improved outcomes inhibitors. The fate subpopulations widely influenced cytokine milieu, versatile roles for B-specific cytokines activating factor attracting chemokine-1/CXCL13, master regulatory role IL-10. Roles cell-specific checkpoints such as TIM-1 emerging could represent potential therapeutic targets. Overall, expanding field tumors holds promise improvement current strategies patient

Language: Английский

The cancer-immunity cycle: Indication, genotype, and immunotype DOI Creative Commons
Ira Mellman, Daniel S. Chen, Thomas Powles

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(10), P. 2188 - 2205

Published: Oct. 1, 2023

The cancer-immunity cycle provides a framework to understand the series of events that generate anti-cancer immune responses. It emphasizes iterative nature response where killing tumor cells by T initiates subsequent rounds antigen presentation and cell stimulation, maintaining active immunity adapting it evolution. Any step can become rate-limiting, rendering system unable control growth. Here, we update based on remarkable progress past decade. Understanding mechanism checkpoint inhibition has evolved, as our view dendritic in sustaining anti-tumor immunity. We additionally account for role microenvironment facilitating, not just suppressing, response, discuss importance considering tumor's immunological phenotype, "immunotype". While these new insights add some complexity cycle, they also provide targets research therapeutic intervention.

Language: Английский

Citations

355
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
CD4+ T cell activation distinguishes response to anti-PD-L1+anti-CTLA4 therapy from anti-PD-L1 monotherapy DOI Creative Commons
Amelie Franken, Michel Bila, Aurelie Mechels

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(3), P. 541 - 558.e7

Published: March 1, 2024

Language: Английский

Citations

33
An immune cell map of human lung adenocarcinoma development reveals an anti-tumoral role of the Tfh-dependent tertiary lymphoid structure DOI Creative Commons
Wei Liu,

Wenhua You,

Zhenwei Lan

et al.

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(3), P. 101448 - 101448

Published: March 1, 2024

The immune responses during the initiation and invasion stages of human lung adenocarcinoma (LUAD) development are largely unknown. Here, we generated a single-cell RNA sequencing map to decipher dynamics LUAD development. We found that T follicular helper (Tfh)-like cells, germinal center B dysfunctional CD8+ cells increase tumor initiation/invasion form tertiary lymphoid structure (TLS) inside tumor. This TLS starts with an aggregation CD4+ generation CXCL13-expressing Tfh-like followed by accumulation then forms cell aggregate. its associated correlated better patient survival. Inhibiting formation Tfh or depletion promotes growth in mouse models. anti-tumoral effect Tfh-dependent is mediated through interleukin-21 (IL-21)-IL-21 receptor signaling. Our study establishes role LUAD.

Language: Английский

Citations

28
Targeting the tumour vasculature: from vessel destruction to promotion DOI
Sophie Guelfi, Kairbaan Hodivala‐Dilke, Gabriele Bergers

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(10), P. 655 - 675

Published: Aug. 29, 2024

Language: Английский

Citations

26
Endothelial cells in tumor microenvironment: insights and perspectives DOI Creative Commons
Patrizia Leone, Eleonora Malerba, Nicola Susca

et al.

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

Published: Feb. 15, 2024

The tumor microenvironment is a highly complex and dynamic mixture of cell types, including tumor, immune endothelial cells (ECs), soluble factors (cytokines, chemokines, growth factors), blood vessels extracellular matrix. Within this network, ECs are not only relevant for controlling fluidity permeability, orchestrating angiogenesis but also regulating the antitumor response. Lining luminal side vessels, check passage molecules into compartment, regulate cellular transmigration, interact with both circulating pathogens innate adaptive cells. Thus, they represent first-line defense system that participates in responses. Tumor-associated involved T priming, activation, proliferation by acting as semi-professional antigen presenting targeting may assist improving functions. Moreover, tumor-associated contribute to development at site tertiary lymphoid structures, which have recently been associated enhanced response checkpoint inhibitors (ICI). When compared normal ECs, abnormal terms phenotype, genetic expression profile, They characterized high proliferative potential ability activate immunosuppressive mechanisms support progression metastatic dissemination. A complete phenotypic functional characterization could be helpful clarify their role within identify EC specific drug targets improve cancer therapy. emerging therapeutic strategies based on combination anti-angiogenic treatments immunotherapy strategies, ICI, CAR bispecific antibodies aim impact block same time increase recruitment activation effector tumor.

Language: Английский

Citations

25
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
Tertiary lymphoid structures in cancer: maturation and induction DOI Creative Commons
Yulu Chen, Yuhao Wu, Guorong Yan

et al.

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

Published: April 16, 2024

Tertiary lymphoid structure (TLS) is an ectopic lymphocyte aggregate formed in peripheral non-lymphoid tissues, including inflamed or cancerous tissue. Tumor-associated TLS serves as a prominent center of antigen presentation and adaptive immune activation within the periphery, which has exhibited positive prognostic value various cancers. In recent years, concept maturity regarding been proposed mature TLS, characterized by well-developed germinal centers, exhibits more potent tumor-suppressive capacity with stronger significance. Meanwhile, evidence showed that can be induced therapeutic interventions during cancer treatments. Thus, evaluation induce its formation are critical issues current research. this review, we aim to provide comprehensive summary existing classifications for strategies capable inducing tumors.

Language: Английский

Citations

18
The interaction of innate immune and adaptive immune system DOI Creative Commons

Ruyuan Wang,

Caini Lan, Kamel Benlagha

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Sept. 15, 2024

The innate immune system serves as the body's first line of defense, utilizing pattern recognition receptors like Toll-like to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific sustained killing via B cells, T antibodies. Traditionally, it has been assumed that activates immunity; however, recent studies have revealed more complex interactions. This review a detailed dissection composition function systems, emphasizing their synergistic roles in physiological pathological contexts, providing new insights into link between these two forms immunity. Precise regulation both systems at same time is beneficial fight against immune-related diseases, for example, cGAS-STING pathway found play an important role infections cancers. In addition, paper summarizes challenges future directions field immunity, including latest single-cell sequencing technologies, CAR-T cell therapy, checkpoint inhibitors. By summarizing developments, aims enhance our understanding complexity interactions perspectives system.

Language: Английский

Citations

18
Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding DOI
Jiancheng Gao, Danling Gu, Kailin Yang

et al.

Cancer Cell, Journal Year: 2025, Volume and Issue: 43(1), P. 122 - 143.e8

Published: Jan. 1, 2025

Language: Английский

Citations

2