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Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses
- Source :
- Cell Reports, Vol 30, Iss 2, Pp 481-496.e6 (2020), 196.e6, Cell Reports
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Summary Loss of p53 function contributes to the development of many cancers. While cell-autonomous consequences of p53 mutation have been studied extensively, the role of p53 in regulating the anti-tumor immune response is still poorly understood. Here, we show that loss of p53 in cancer cells modulates the tumor-immune landscape to circumvent immune destruction. Deletion of p53 promotes the recruitment and instruction of suppressive myeloid CD11b+ cells, in part through increased expression of CXCR3/CCR2-associated chemokines and macrophage colony-stimulating factor (M-CSF), and attenuates the CD4+ T helper 1 (Th1) and CD8+ T cell responses in vivo. p53-null tumors also show an accumulation of suppressive regulatory T (Treg) cells. Finally, we show that two key drivers of tumorigenesis, activation of KRAS and deletion of p53, cooperate to promote immune tolerance.<br />Graphical Abstract<br />Highlights • Tumor-specific loss of p53 delays tumor rejection in immune-competent hosts • p53 loss increases myeloid infiltration through enhanced cytokine secretion • The increase in Treg cells in response to loss of p53 is independent of Kras mutation • Kras mutations coordinate with p53 loss to regulate myeloid recruitment<br />TP53 is one of the most frequently mutated genes in cancer; however, its significance in controlling tumor-immune crosstalk is not fully understood. Blagih et al. highlight a key role for tumor-associated loss of p53, a common oncogenic event, in regulating myeloid and T cell responses.
- Subjects :
- p53
Myeloid
PROMOTES
BLOCKADE
PROGRESSION
MICROENVIRONMENT
0601 Biochemistry and Cell Biology
medicine.disease_cause
T-Lymphocytes, Regulatory
Immune tolerance
Mice
0302 clinical medicine
Ecology,Evolution & Ethology
Macrophage
MACROPHAGES
lcsh:QH301-705.5
Chemical Biology & High Throughput
Human Biology & Physiology
0303 health sciences
Genome Integrity & Repair
3. Good health
medicine.anatomical_structure
myeloid cells
030220 oncology & carcinogenesis
GROWTH
Genetics & Genomics
Life Sciences & Biomedicine
tumor
T cell
IMMUNITY
Biology
Article
General Biochemistry, Genetics and Molecular Biology
Signalling & Oncogenes
03 medical and health sciences
Immune system
INFLAMMATION
medicine
Animals
Humans
Computational & Systems Biology
030304 developmental biology
Science & Technology
Cell Biology
Tumour Biology
TUMOR-SUPPRESSOR P53
T cell response
Metabolism
lcsh:Biology (General)
1116 Medical Physiology
Cancer cell
Kras
Cancer research
Tumor Suppressor Protein p53
Carcinogenesis
CD8
RAS
Subjects
Details
- Language :
- English
- ISSN :
- 22111247
- Volume :
- 30
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....739f1f60383121c624cb1664777663b3