Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways DOI Creative Commons
Lavinia Spain, Alexander Coulton, Irene Lobón

et al.

Cancer Discovery, Journal Year: 2023, Volume and Issue: 13(6), P. 1364 - 1385

Published: March 28, 2023

Abstract Understanding the evolutionary pathways to metastasis and resistance immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present most comprehensive intrapatient metastatic dataset assembled date as part of Posthumous Evaluation Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent doubling widespread loss heterozygosity, often involving antigen-presentation machinery. found KIT extrachromosomal DNA may have contributed lack response a KIT-driven melanoma. At lesion-level, MYC amplifications were enriched ICI nonresponders. Single-cell revealed polyclonal seeding metastases originating clones with different ploidy one patient. Finally, that brain diverged early molecular evolution emerge late disease. Overall, our study illustrates diverse landscape advanced Significance: Despite treatment advances, remains deadly disease at stage IV. Through dense sampling combined extensive multiomic profiling, elucidates many mechanisms melanomas use evade immune system, whether through mutations, copy-number alterations, or DNA. See related commentary by Shain, p. 1294. This article highlighted In Issue feature, 1275

Language: Английский

The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth DOI Creative Commons
Karin E. de Visser, Johanna A. Joyce

Cancer Cell, Journal Year: 2023, Volume and Issue: 41(3), P. 374 - 403

Published: March 1, 2023

Language: Английский

Citations

1514
Biology of lung macrophages in health and disease DOI Creative Commons
Helena Aegerter, Bart N. Lambrecht, Claudia Jakubzick

et al.

Immunity, Journal Year: 2022, Volume and Issue: 55(9), P. 1564 - 1580

Published: Sept. 1, 2022

Language: Английский

Citations

317
A timeline of tumour-associated macrophage biology DOI
Luca Cassetta, Jeffrey W. Pollard

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(4), P. 238 - 257

Published: Feb. 15, 2023

Language: Английский

Citations

280
Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance DOI Creative Commons
Shujing Wang, Jingrui Wang, Zhiqiang Chen

et al.

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: Feb. 10, 2024

Abstract Tumor drug resistance emerges from the interaction of two critical factors: tumor cellular heterogeneity and immunosuppressive nature microenvironment (TME). Tumor-associated macrophages (TAMs) constitute essential components TME. M2-like TAMs are in facilitating metastasis as well augmenting tumors. This review encapsulates mechanisms that use to promote resistance. We also describe emerging therapeutic strategies currently targeting combination with other antitumor drugs, some still undergoing clinical trial evaluation. Furthermore, we summarize analyze various existing approaches for developing novel drugs target overcome resistance, highlighting how can effectively stop growth, metastasis,

Language: Английский

Citations

140
Roles of macrophages in tumor development: a spatiotemporal perspective DOI Creative Commons

Mathilde Bied,

William W. Ho, Florent Ginhoux

et al.

Cellular and Molecular Immunology, Journal Year: 2023, Volume and Issue: 20(9), P. 983 - 992

Published: July 10, 2023

Abstract Macrophages are critical regulators of tissue homeostasis but also abundant in the tumor microenvironment (TME). In both primary tumors and metastases, such tumor-associated macrophages (TAMs) seem to support development. While we know that TAMs dominant immune cells TME, their vast heterogeneity associated functions only just being unraveled. this review, outline various known TAM populations found thus far delineate specialized roles with main stages cancer progression. We discuss how may prime premetastatic niche enable growth a metastasis then subsequent metastasis-associated can secondary growth. Finally, speculate on challenges remain be overcome research.

Language: Английский

Citations

127
Targeting IRG1 reverses the immunosuppressive function of tumor-associated macrophages and enhances cancer immunotherapy DOI Creative Commons
Yujia Chen, Guan-Nan Li,

Xian-Jing Li

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(17)

Published: April 28, 2023

Immune-responsive gene 1 (IRG1) encodes aconitate decarboxylase (ACOD1) that catalyzes the production of itaconic acids (ITAs). The anti-inflammatory function IRG1/ITA has been established in multiple pathogen models, but very little is known cancer. Here, we show IRG1 expressed tumor-associated macrophages (TAMs) both human and mouse tumors. Mechanistically, tumor cells induce Irg1 expression by activating NF-κB pathway, ITA produced ACOD1 inhibits TET DNA dioxygenases to dampen inflammatory genes infiltration CD8+ T into sites. Deletion mice suppresses growth types enhances efficacy anti-PD-(L)1 immunotherapy. Our study provides a proof concept potential target for immune-oncology drugs IRG1-deficient represent potent cell therapy strategy cancer treatment even pancreatic tumors are resistant cell-based

Language: Английский

Citations

83
Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma DOI
Alessandra De Leo, Alessio Ugolini, Xiaoqing Yu

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(5), P. 1105 - 1123.e8

Published: May 1, 2024

Language: Английский

Citations

57
Spatial transcriptomics of B cell and T cell receptors reveals lymphocyte clonal dynamics DOI
Camilla Engblom, Kim Thrane, Qirong Lin

et al.

Science, Journal Year: 2023, Volume and Issue: 382(6675)

Published: Dec. 7, 2023

The spatial distribution of lymphocyte clones within tissues is critical to their development, selection, and expansion. We have developed transcriptomics variable, diversity, joining (VDJ) sequences (Spatial VDJ), a method that maps B cell T receptor in human tissue sections. Spatial VDJ captures match canonical distributions amplifies clonal confirmed by orthogonal methods. found congruency between paired chains, computational framework predict pairs, linked the expansion distinct different tumor-associated gene expression programs. delineates diversity lineage trajectories anatomical niche. Thus, architecture across tissues, providing platform harness for therapy.

Language: Английский

Citations

43
The CAR macrophage cells, a novel generation of chimeric antigen-based approach against solid tumors DOI Creative Commons
Kaveh Hadiloo,

Siavash Taremi,

Mahmood Heidari

et al.

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: Nov. 28, 2023

Abstract Today, adoptive cell therapy has many successes in cancer therapy, and this subject is brilliant using chimeric antigen receptor T cells. The CAR with its FDA-approved drugs, could treat several types of hematological malignancies thus be very attractive for treating solid cancer. Unfortunately, the cannot functional cancers due to unique features. This treatment method harmful adverse effects that limit their applications, so novel treatments must use new cells like NK cells, NKT macrophage Among these innate features, are more tumor seem a better candidate prior methods. have vital roles microenvironment and, direct effect, can eliminate efficiently. In addition, being part immune system, attended sites. With high infiltration, modulations effective. review investigates last achievements CAR-macrophage future immunotherapy method.

Language: Английский

Citations

42
Modulation of the tumor microenvironment and mechanism of immunotherapy-based drug resistance in breast cancer DOI Creative Commons
Moumita Kundu, Ramesh Butti, Venketesh K. Panda

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 7, 2024

Abstract Breast cancer, the most frequent female malignancy, is often curable when detected at an early stage. The treatment of metastatic breast cancer more challenging and may be unresponsive to conventional therapy. Immunotherapy crucial for treating but its resistance a major limitation. tumor microenvironment (TME) vital in modulating immunotherapy response. Various microenvironmental components, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), are involved TME modulation cause resistance. This review highlights role stromal microenvironment, including involvement CAF-TAM interaction, alteration metabolism leading failure, other latest strategies, high throughput genomic screening, single-cell spatial omics techniques identifying immune genes regulating emphasizes therapeutic approach overcome through CAF reprogramming, TAM polarization, metabolism, alterations.

Language: Английский

Citations

41