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The role of innate immune signals in antitumor immunity.

Jinushi M - Oncoimmunology (2012)

Bottom Line: Recent evidence demonstrates that these pattern-sensing systems are also applicable to the recognition of tumor-derived stress-related factors.In particular, toll-like receptors and cytosolic sensors for DNA and RNA recognition utilize endogenous host elements containing microbial components, danger-associated molecules, and/or nucleic acids to stimulate innate signaling pathways and generate protective immune responses against nascent tumors in animal models and humans.In this review, we describe recent advances and perspectives about antitumor mechanisms and clinical application of innate immune signals and pathways.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Infection-Associated Cancer; Institute for Genetic Medicine; Hokkaido University; Sapporo, Hokkaido, Japan.

ABSTRACT
Innate immunity serves as a first line of defense against infectious agents, and germ-line-encoded pattern recognition receptors detect stressed and infected cells and elicit potent effector activities that accomplish efficient microbe containment. Recent evidence demonstrates that these pattern-sensing systems are also applicable to the recognition of tumor-derived stress-related factors. In particular, toll-like receptors and cytosolic sensors for DNA and RNA recognition utilize endogenous host elements containing microbial components, danger-associated molecules, and/or nucleic acids to stimulate innate signaling pathways and generate protective immune responses against nascent tumors in animal models and humans. In this review, we describe recent advances and perspectives about antitumor mechanisms and clinical application of innate immune signals and pathways.

No MeSH data available.


Related in: MedlinePlus

Figure 3. NLRP3-mediated antitumor responses. ATP and PRRs released from dying tumor cells consequent to cytotoxic therapies send the “find-me” signals to dendritic cells to facilitate the uptake of apoptotic tumor cells, and trigger the ROS production to activate NLRP3-mediated inflammasome pathways. The resultant activation of inflammasome results in the release of IL-1β, which may contribute to the tumor-specific CTL responses.
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Figure 3: Figure 3. NLRP3-mediated antitumor responses. ATP and PRRs released from dying tumor cells consequent to cytotoxic therapies send the “find-me” signals to dendritic cells to facilitate the uptake of apoptotic tumor cells, and trigger the ROS production to activate NLRP3-mediated inflammasome pathways. The resultant activation of inflammasome results in the release of IL-1β, which may contribute to the tumor-specific CTL responses.

Mentions: Besides the role of NLRP3 in regulating inflammation and colon cancer, inflammasomes may be associated with broad modes of carcinogenesis and antitumor immunity. Recent report implicates that NLRP agonist ATP plays a role in recruiting phagocytes to facilitate phagocytic removal of apoptotic cells.44 In addition, ATP further boosts innate responses in coordination with PPRs by interacting with thioredoxin-interacting protein TXNIP and generating ROS.45 In this regard, it is possible that upon the recognition of dying tumor cells with phagocytosis, the release of ATP from dying tumor cells senses DCs to activate NLRP3 inflammasome and secrete IL-1β, by which antitumor effector CD8+ T cells were efficiently primed to induce antitumor immunity (Fig. 3). Indeed, recent study validated the role of ATP from chemotherapy-sensitized tumor cells in stimulating NLRP3-mediated IL-1β and tumor-specific CD8+T cell responses.46 In addition, the oncogenic pathways, such as Bcl-2 anti-apoptotic families, as well as autophagic responses, may influence the biologic activities of inflammasome pathways by interacting with key signaling components,47,48 underscoring the broad and heterogeneous functions of inflammasomes in regulating various modes of stress responses in tumor cells.


The role of innate immune signals in antitumor immunity.

Jinushi M - Oncoimmunology (2012)

Figure 3. NLRP3-mediated antitumor responses. ATP and PRRs released from dying tumor cells consequent to cytotoxic therapies send the “find-me” signals to dendritic cells to facilitate the uptake of apoptotic tumor cells, and trigger the ROS production to activate NLRP3-mediated inflammasome pathways. The resultant activation of inflammasome results in the release of IL-1β, which may contribute to the tumor-specific CTL responses.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376990&req=5

Figure 3: Figure 3. NLRP3-mediated antitumor responses. ATP and PRRs released from dying tumor cells consequent to cytotoxic therapies send the “find-me” signals to dendritic cells to facilitate the uptake of apoptotic tumor cells, and trigger the ROS production to activate NLRP3-mediated inflammasome pathways. The resultant activation of inflammasome results in the release of IL-1β, which may contribute to the tumor-specific CTL responses.
Mentions: Besides the role of NLRP3 in regulating inflammation and colon cancer, inflammasomes may be associated with broad modes of carcinogenesis and antitumor immunity. Recent report implicates that NLRP agonist ATP plays a role in recruiting phagocytes to facilitate phagocytic removal of apoptotic cells.44 In addition, ATP further boosts innate responses in coordination with PPRs by interacting with thioredoxin-interacting protein TXNIP and generating ROS.45 In this regard, it is possible that upon the recognition of dying tumor cells with phagocytosis, the release of ATP from dying tumor cells senses DCs to activate NLRP3 inflammasome and secrete IL-1β, by which antitumor effector CD8+ T cells were efficiently primed to induce antitumor immunity (Fig. 3). Indeed, recent study validated the role of ATP from chemotherapy-sensitized tumor cells in stimulating NLRP3-mediated IL-1β and tumor-specific CD8+T cell responses.46 In addition, the oncogenic pathways, such as Bcl-2 anti-apoptotic families, as well as autophagic responses, may influence the biologic activities of inflammasome pathways by interacting with key signaling components,47,48 underscoring the broad and heterogeneous functions of inflammasomes in regulating various modes of stress responses in tumor cells.

Bottom Line: Recent evidence demonstrates that these pattern-sensing systems are also applicable to the recognition of tumor-derived stress-related factors.In particular, toll-like receptors and cytosolic sensors for DNA and RNA recognition utilize endogenous host elements containing microbial components, danger-associated molecules, and/or nucleic acids to stimulate innate signaling pathways and generate protective immune responses against nascent tumors in animal models and humans.In this review, we describe recent advances and perspectives about antitumor mechanisms and clinical application of innate immune signals and pathways.

View Article: PubMed Central - PubMed

Affiliation: Research Center for Infection-Associated Cancer; Institute for Genetic Medicine; Hokkaido University; Sapporo, Hokkaido, Japan.

ABSTRACT
Innate immunity serves as a first line of defense against infectious agents, and germ-line-encoded pattern recognition receptors detect stressed and infected cells and elicit potent effector activities that accomplish efficient microbe containment. Recent evidence demonstrates that these pattern-sensing systems are also applicable to the recognition of tumor-derived stress-related factors. In particular, toll-like receptors and cytosolic sensors for DNA and RNA recognition utilize endogenous host elements containing microbial components, danger-associated molecules, and/or nucleic acids to stimulate innate signaling pathways and generate protective immune responses against nascent tumors in animal models and humans. In this review, we describe recent advances and perspectives about antitumor mechanisms and clinical application of innate immune signals and pathways.

No MeSH data available.


Related in: MedlinePlus