Cancer genome and tumor microenvironment: Reciprocal crosstalk shapes lung cancer plasticity
Open Access
- 8 September 2022
- journal article
- review article
- Published by eLife Sciences Publications, Ltd in eLife
- Vol. 11
Abstract
Lung cancer classification and treatment has been revolutionized by improving our understanding of driver mutations and the introduction of tumor microenvironment (TME)-associated immune checkpoint inhibitors. Despite the significant improvement of lung cancer patient survival in response to either oncogene-targeted therapy or anticancer immunotherapy, many patients show initial or acquired resistance to these new therapies. Recent advances in genome sequencing reveal that specific driver mutations favor the development of an immunosuppressive TME phenotype, which may result in unfavorable outcomes in lung cancer patients receiving immunotherapies. Clinical studies with follow-up after immunotherapy, assessing oncogenic driver mutations and the TME immune profile, not only reveal the underlying potential molecular mechanisms in the resistant lung cancer patients but also hold the key to better treatment choices and the future of personalized medicine. In this review, we discuss the crosstalk between cancer cell genomic features and the TME to reveal the impact of genetic alterations on the TME phenotype. We also provide insights into the regulatory role of cellular TME components in defining the genetic landscape of cancer cells during tumor development.Keywords
Funding Information
- Cardio-Pulmonary Institute (project 390649896)
- Deutsche Forschungsgemeinschaft (SA 1923/7-1)
- German Center for Lung Research
- State of Hesse (LOEWE-iCANx)
- Bundesministerium für Forschung, Technologie und Raumfahrt (KMU-innovativ-22)
- Max Planck Society
- Deutsche Forschungsgemeinschaft (TRR81/3)
- Deutsche Forschungsgemeinschaft (SFB1213)
- Deutsche Forschungsgemeinschaft (SFB1021)
- Deutsche Forschungsgemeinschaft (GRK 2573)
- Deutsche Forschungsgemeinschaft (SFB1213)
- Deutsche Forschungsgemeinschaft (project 284237345)
- Deutsche Forschungsgemeinschaft (project 109546710)
- Deutsche Forschungsgemeinschaft (project 268555672)
- Deutsche Forschungsgemeinschaft (project 268555672)
- Deutsche Forschungsgemeinschaft (project 197785619)
- Deutsche Forschungsgemeinschaft (project 416910386)
- Deutsche Forschungsgemeinschaft (KR1143/9-2)
This publication has 168 references indexed in Scilit:
- Signatures of mutational processes in human cancerNature, 2013
- LKB1 Inactivation Dictates Therapeutic Response of Non-Small Cell Lung Cancer to the Metabolism Drug PhenforminCancer Cell, 2013
- Treating inflammation by blocking interleukin-1 in a broad spectrum of diseasesNature Reviews Drug Discovery, 2012
- Clonal evolution in cancerNature, 2012
- Hallmarks of Cancer: The Next GenerationCell, 2011
- Requirement for NF-κB signalling in a mouse model of lung adenocarcinomaNature, 2009
- Boveri revisited: chromosomal instability, aneuploidy and tumorigenesisNature Reviews Molecular Cell Biology, 2009
- Is NF-κB a good target for cancer therapy? Hopes and pitfallsNature Reviews Drug Discovery, 2009
- Regulation of immune responses by L-arginine metabolismNature Reviews Immunology, 2005
- The Hallmarks of CancerCell, 2000