Related Experiment Video

Updated: Feb 7, 2026

Using RNA-interference to Investigate the Innate Immune Response in Mouse Macrophages
12:47

Using RNA-interference to Investigate the Innate Immune Response in Mouse Macrophages

Published on: November 3, 2014

12.2K

Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses

Israel Cañadas1, Rohit Thummalapalli1, Jong Wook Kim1,2

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Nature Medicine
|July 25, 2018
PubMed

Insights

Certain endogenous retroviruses (ERVs) can be reactivated by cancer therapies, triggering innate immune signaling and promoting tumor growth. This discovery offers new avenues for cancer immunotherapy strategies.

Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Mesenchymal tumor cells secrete factors that enhance tumor progression and treatment resistance.
  • The precise mechanisms driving these pro-tumorigenic effects and treatment resistance are not fully understood.
  • Endogenous retroviruses (ERVs) are implicated in various cellular processes, but their role in cancer-associated immune signaling is emerging.

Purpose of the Study:

  • To identify specific endogenous retroviruses (ERVs) involved in promoting tumor-associated immune signaling.
  • To elucidate the molecular mechanisms by which these ERVs activate innate immune pathways.
  • To investigate the clinical relevance of these ERVs in human cancers and their potential as therapeutic targets.

Main Methods:

  • Identification and characterization of a novel subclass of ERVs, termed Stimulated 3 prime antisense retroviral coding sequences (SPARCS).
  • Analysis of SPARCS' genomic location, orientation, and transcriptional regulation by STAT1 and EZH2.
  • Investigation of SPARCS-mediated double-stranded RNA generation and subsequent activation of innate immune sensors (MAVS, STING) and signaling pathways (TBK1, IRF3, STAT1).
  • Correlation of SPARCS expression with tumor markers (MHC class I, mesenchymal markers, AXL/MET) and immune infiltration in human tumors and cell lines.

Main Results:

  • A subclass of ERVs, SPARCS, was identified, located in 3' untranslated regions and regulated by STAT1 and EZH2.
  • IFN-γ exposure induces bi-directional transcription leading to double-stranded RNA production and activation of MAVS/STING-TBK1/IRF3/STAT1 signaling.
  • SPARCS expression positively correlates with MHC class I, mesenchymal markers, and AXL/MET expression, and inversely with EZH2.
  • SPARCS-high tumors show immune infiltration but also exhibit immune-suppressive features.

Conclusions:

  • Derepression of SPARCS triggers pathologic innate immune signaling in cancer cells, contributing to a pro-tumorigenic and immune-suppressed microenvironment.
  • SPARCS represent a novel mechanism linking ERV activity to cancer progression and immune evasion.
  • Targeting SPARCS-mediated signaling pathways may offer a promising strategy for enhancing cancer immunotherapy.

More Related Videos

Author Spotlight: Establishing Mixed Neuronal and Glial Cell Cultures from Embryonic Mouse Brains to Study Infection and Innate Immunity07:41

Author Spotlight: Establishing Mixed Neuronal and Glial Cell Cultures from Embryonic Mouse Brains to Study Infection and Innate Immunity

Published on: June 30, 2023

3.7K
Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

3.8K

Related Concept Videos

Retroviruses02:33

Retroviruses

Retroviruses and retrotransposons both insert copies of their genetic elements into the genome of the host cell. Thus, the viral genes are passed on when the host genome is replicated or translated. A typical retroviral DNA sequence contains 3-4 genes that encode the different proteins required for its structural assembly and function as a molecular parasite. This DNA is transcribed into a single mRNA, which is very similar in structure to conventional mRNAs, i.e., it is capped at the 5’...
15.0K
What is the Immune System?01:38

What is the Immune System?

Overview
130.8K
Introduction to Innate and Adaptive Immunity01:21

Introduction to Innate and Adaptive Immunity

The human immune system is a complex defense mechanism that protects the body from harmful pathogens and foreign substances. It comprises two crucial components: innate and adaptive immunity.
Innate immunity is the body's natural, nonspecific defense system that acts quickly to protect against pathogens. It incorporates physical barriers like skin and mucous membranes and cellular elements such as phagocytes and natural killer cells. This part of our immune system provides an immediate,...
9.7K
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
9.3K
Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
49.7K
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
7.0K