Pro-necrotic molecules impact local immunosurveillance in human breast cancer

Oncoimmunology
Gautier StollGuido Kroemer

Abstract

Necrosis culminates in spilling cellular content through the permeabilized plasma membrane, thereby releasing potentially immunostimulatory molecules in the pericellular space of dead cells. Accordingly, molecules involved in necroptotic signaling, such as receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase-like (MLKL) have been found to stimulate anticancer immune responses in mouse models of chemotherapy. mRNAs encoding prominent pro-necrotic gene products (RIPK1, RIPK3, MLKL, PGAM5 and DFNA5) were correlated with immune-related metagenes in several cancer types (breast, colorectal, lung, ovary, melanoma), revealing the strongest associations in breast cancer. In two independent breast cancer cohorts, the expression of MLKL and DFNA5 was decreased at the mRNA levels in tumor as compared with normal tissues. Moreover, MLKL expression exhibited a strong positive correlation with genes reflecting the presence of B, NK and T lymphocytes in the tumor bed, in multiple distinct breast cancer subtypes. In contrast, the positive correlation between RIPK3 and lymphoid cells was restricted to HER2+ and triple negative/basal-like breast cancer. Moreover, the expression of DFNA5, which mediates post-apo...Continue Reading

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Citations

Jul 26, 2017·Nature Reviews. Clinical Oncology·Wolf H FridmanGuido Kroemer
Oct 14, 2017·Immunological Reviews·Olga KryskoDmitri V Krysko
Apr 24, 2018·Clinical Epigenetics·Lieselot CroesKen Op de Beeck
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Aug 8, 2020·Nature Reviews. Clinical Oncology·Lorenzo GalluzziGuido Kroemer
Jan 23, 2021·Cancers·Vanessa CastelliMichele d'Angelo
Feb 12, 2021·Cancers·Laura Della TorreLucia Altucci
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May 7, 2021·Cell Death and Differentiation·Sofie MartensNozomi Takahashi
Jul 25, 2021·Cancers·Xiuxia LuXing Zhang
Sep 23, 2021·Cell Biology International·Mingcheng LiuLiancheng Lei
Oct 17, 2021·Cellular and Molecular Life Sciences : CMLS·Shanhui LiuJiwang Zhang
Dec 7, 2021·Frontiers in Pharmacology·Wen LiLining Miao
Jan 7, 2022·Annals of Hematology·Zhao XuPeng Liu

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Software Mentioned

CIBERSORT
CIBSERSORT
MCP
IMMUNOME
R
METABRIC
GSEA
- package
- counter
GseaPreranked

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