T follicular helper cells in cancer DOI Creative Commons
Nicolás Gutiérrez-Melo, Dirk Baumjohann

Trends in cancer, Journal Year: 2023, Volume and Issue: 9(4), P. 309 - 325

Published: Jan. 14, 2023

T follicular helper (Tfh) cells provide essential help to B for effective antibody-mediated immune responses. Although the crucial function of these CD4+ in infection and vaccination is well established, their involvement cancer only beginning emerge. Increased numbers Tfh cell-derived or cell-associated malignancies are often associated with an unfavorable outcome, whereas various solid organ tumor types non-lymphocytic origin, presence frequently coincides a better prognosis. We discuss recent advances understanding how cell crosstalk CD8+ secondary tertiary lymphoid structures (TLS) enhances antitumor immunity, but may also exacerbate immune-related adverse events (irAEs) such as autoimmunity during checkpoint blockade (ICB) immunotherapy.

Language: Английский

Clinical relevance of tumour-associated macrophages DOI
Mikaël J. Pittet, Olivier Michielin, Denis Migliorini

et al.

Nature Reviews Clinical Oncology, Journal Year: 2022, Volume and Issue: 19(6), P. 402 - 421

Published: March 30, 2022

Language: Английский

Citations

481
B cells and tertiary lymphoid structures as determinants of tumour immune contexture and clinical outcome DOI
Wolf H. Fridman, Maxime Meylan, Florent Petitprez

et al.

Nature Reviews Clinical Oncology, Journal Year: 2022, Volume and Issue: 19(7), P. 441 - 457

Published: April 1, 2022

Language: Английский

Citations

410
Deciphering breast cancer: from biology to the clinic DOI Creative Commons
Emma Nolan, Geoffrey J. Lindeman, Jane E. Visvader

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(8), P. 1708 - 1728

Published: March 16, 2023

Language: Английский

Citations

372
Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses DOI Creative Commons
Can Cui, Jiawei Wang, Eric Fagerberg

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(25), P. 6101 - 6118.e13

Published: Nov. 30, 2021

Language: Английский

Citations

321
Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation DOI Creative Commons
Meng‐Ling Wu,

Qianrui Huang,

Yao Xie

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: March 12, 2022

Abstract Immune checkpoint molecules are promising anticancer targets, among which therapeutic antibodies targeting the PD-1/PD-L1 pathway have been widely applied to cancer treatment in clinical practice and great potential. However, this is greatly limited by its low response rates certain cancers, lack of known biomarkers, immune-related toxicity, innate acquired drug resistance, etc. Overcoming these limitations would significantly expand applications blockade improve rate survival time patients. In present review, we first illustrate biological mechanisms immune checkpoints their role healthy system as well tumor microenvironment (TME). The inhibits effect T cells TME, turn regulates expression levels PD-1 PD-L1 through multiple mechanisms. Several strategies proposed solve anti-PD-1/PD-L1 treatment, including combination therapy with other standard treatments, such chemotherapy, radiotherapy, targeted therapy, anti-angiogenic immunotherapies even diet control. Downregulation TME via pharmacological or gene regulation methods improves efficacy treatment. Surprisingly, recent preclinical studies shown that upregulation also blockade. Immunotherapy a strategy provides novel insight into applications. This review aims guide development more effective less toxic immunotherapies.

Language: Английский

Citations

310
Cytotoxic CD4+ T cells in cancer: Expanding the immune effector toolbox DOI Creative Commons
David Y. Oh, Lawrence Fong

Immunity, Journal Year: 2021, Volume and Issue: 54(12), P. 2701 - 2711

Published: Dec. 1, 2021

Cytotoxic T cells are important effectors of anti-tumor immunity. While tumor killing is ascribed to CD8+ cell function, pre-clinical and clinical studies have identified intra-tumoral CD4+ that possess cytotoxic programs can directly kill cancer cells. found in other disease settings including infection autoimmunity. Here, we review the phenotypic functional characteristics non-cancer contexts. We conduct a comparative examination cytolytic mechanisms across states synthesize features define these independent context. discuss regulatory driving ontogeny effector function evidence for relevance cancer. In this context, highlight gaps understanding biology as well potential use immunotherapies specific cancers.

Language: Английский

Citations

299
New opportunities and challenges of natural products research: When target identification meets single-cell multiomics DOI
Yuyu Zhu, Zijun Ouyang, Haojie Du

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2022, Volume and Issue: 12(11), P. 4011 - 4039

Published: Aug. 27, 2022

Language: Английский

Citations

264
Spatially informed clustering, integration, and deconvolution of spatial transcriptomics with GraphST DOI Creative Commons
Yahui Long, Kok Siong Ang, Mengwei Li

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: March 1, 2023

Abstract Spatial transcriptomics technologies generate gene expression profiles with spatial context, requiring spatially informed analysis tools for three key tasks, clustering, multisample integration, and cell-type deconvolution. We present GraphST, a graph self-supervised contrastive learning method that fully exploits data to outperform existing methods. It combines neural networks learn informative discriminative spot representations by minimizing the embedding distance between adjacent spots vice versa. demonstrated GraphST on multiple tissue types technology platforms. achieved 10% higher clustering accuracy better delineated fine-grained structures in brain embryo tissues. is also only can jointly analyze slices vertical or horizontal integration while correcting batch effects. Lastly, superior deconvolution capture niches like lymph node germinal centers exhausted tumor infiltrating T cells breast tissue.

Language: Английский

Citations

249
Applications of single-cell RNA sequencing in drug discovery and development DOI Creative Commons
Bram Van de Sande, Joon Sang Lee, Euphemia Mutasa-Gottgens

et al.

Nature Reviews Drug Discovery, Journal Year: 2023, Volume and Issue: 22(6), P. 496 - 520

Published: April 28, 2023

Single-cell technologies, particularly single-cell RNA sequencing (scRNA-seq) methods, together with associated computational tools and the growing availability of public data resources, are transforming drug discovery development. New opportunities emerging in target identification owing to improved disease understanding through cell subtyping, highly multiplexed functional genomics screens incorporating scRNA-seq enhancing credentialling prioritization. ScRNA-seq is also aiding selection relevant preclinical models providing new insights into mechanisms action. In clinical development, can inform decision-making via biomarker for patient stratification more precise monitoring response progression. Here, we illustrate how methods being applied key steps discuss ongoing challenges their implementation pharmaceutical industry. There have been significant recent advances development remarkable Ferran colleagues primarily pipeline, from decision-making. Ongoing potential future directions discussed.

Language: Английский

Citations

213
Breast cancer: an up‐to‐date review and future perspectives DOI Creative Commons
Ruoxi Hong, Binghe Xu

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(10), P. 913 - 936

Published: Sept. 8, 2022

Breast cancer is the most common worldwide. The occurrence of breast associated with many risk factors, including genetic and hereditary predisposition. cancers are highly heterogeneous. Treatment strategies for vary by molecular features, activation human epidermal growth factor receptor 2 (HER2), hormonal receptors (estrogen [ER] progesterone [PR]), gene mutations (e.g., 1/2 [BRCA1/2] phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [PIK3CA]) markers immune microenvironment tumor-infiltrating lymphocyte [TIL] programmed death-ligand 1 [PD-L1]). Early-stage considered curable, which local-regional therapies (surgery radiotherapy) cornerstone, systemic therapy given before or after surgery when necessary. Preoperative neoadjuvant therapy, targeted drugs checkpoint inhibitors, has become standard care early-stage HER2-positive triple-negative cancer, followed risk-adapted post-surgical strategies. For ER-positive early endocrine 5-10 years essential. Advanced distant metastases currently incurable. Systemic in this setting include agents, such as CDK4/6 inhibitors phosphoinositide (PI3K) hormone receptor-positive disease, anti-HER2 poly(ADP-ribose) polymerase BRCA1/2 mutation carriers immunotherapy part disease. Innovation technologies precision medicine may guide individualized treatment escalation de-escalation future. In review, we summarized latest scientific information discussed future perspectives on cancer.

Language: Английский

Citations

209