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Manuscript Submission Deadline 01 March 2024

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Pattern recognition receptors (PRRs) were originally identified as immune cell receptors for pathogen-associated molecular patterns (PAMPs), which are molecules harbored by bacteria, viruses, or parasites. It has been shown that PRRs also recognize products of stressed cells or damaged tissues, named damage-associated molecular patterns (DAMPs). Therefore, they are key sensors in the response against microbial infections and are relevant in the process of sterile inflammation. One group of PRRs, toll-like receptors (TLRs), comprise a family of ten (TLR1-10) or twelve (TLR1-9, 11-13) molecules (human and mouse respectively) which are expressed on the plasma or endosomal membranes of eukaryotic cells. Interaction of TLRs with their agonists will typically activate signaling pathways associated with inflammation and immune responses. Albeit originally described as immune cell receptors, it has been shown that TLRs (and other PRRs) are present and functional in non-immune cells, among them, cancer cells.

In the last decades, it has been demonstrated that interaction of TLRs expressed by tumor cells with their agonists can either induce anti-tumor or protumor effects, depending on the TLR molecule, tumor type and the nature of the tumor microenvironment. TLR agonists have been used as adjuvants for antitumor vaccines and have been used to activate immune cells in vivo for immunotherapeutic approaches. Considering that TLRs are expressed by cancer cells, it becomes relevant to unravel the role of PRRs in promoting tumor growth; shaping the tumor microenvironment (i.e., promoting changes in the tumor microenvironment via immune cell recruitment or extracellular matrix remodeling); regulating metabolic functions of tumor cells or inducing immunogenic cell death (i.e., in the context of oncolytic virotherapy).

Unraveling the role of TLRs expressed by transformed cells on tumor biology will help define therapeutic approaches against cancer beyond the proposed use of TLR agonists as activators of immune cells for immunotherapeutic interventions.

This Research Topic accepts Original Research, Systematic Review, Methods, Review and Mini-Review, Perspective, Case Report, Brief Research Report, Data Report. We welcome manuscripts focusing on, but not limited to, the following sub-topics:
• Role of Toll-like receptors expressed by transformed cells on tumor progression.
• Role of Toll-like receptors expressed by transformed cells on cell metabolism.
• Toll-like receptor ligands as inducers of immunogenic cell death, including activation via oncolytic therapies.
• Toll-like receptors expressed by transformed cells as targets for cancer therapeutics.
• Role of Toll-like receptors expressed by transformed cells in shaping the tumor microenvironment (immune cell infiltration, extracellular matrix remodeling)
• Signaling pathways activated by TLR agonists in cancer cells.
• Toll-like receptors in cancer drug resistance.

Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation are considered out of scope of this section.

Topic editor Dr. Kelly McCall is a founding member of the AOHBio Corporation. All other Topic Editors declare no competing interests with regards to the Research Topic subject.

Keywords: toll-like receptors, TLR, tumor microenvironment, TME, Immunogenic cell death, TLR activation, tumor metabolism, signaling pathways, tumor extracellular matrix


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Pattern recognition receptors (PRRs) were originally identified as immune cell receptors for pathogen-associated molecular patterns (PAMPs), which are molecules harbored by bacteria, viruses, or parasites. It has been shown that PRRs also recognize products of stressed cells or damaged tissues, named damage-associated molecular patterns (DAMPs). Therefore, they are key sensors in the response against microbial infections and are relevant in the process of sterile inflammation. One group of PRRs, toll-like receptors (TLRs), comprise a family of ten (TLR1-10) or twelve (TLR1-9, 11-13) molecules (human and mouse respectively) which are expressed on the plasma or endosomal membranes of eukaryotic cells. Interaction of TLRs with their agonists will typically activate signaling pathways associated with inflammation and immune responses. Albeit originally described as immune cell receptors, it has been shown that TLRs (and other PRRs) are present and functional in non-immune cells, among them, cancer cells.

In the last decades, it has been demonstrated that interaction of TLRs expressed by tumor cells with their agonists can either induce anti-tumor or protumor effects, depending on the TLR molecule, tumor type and the nature of the tumor microenvironment. TLR agonists have been used as adjuvants for antitumor vaccines and have been used to activate immune cells in vivo for immunotherapeutic approaches. Considering that TLRs are expressed by cancer cells, it becomes relevant to unravel the role of PRRs in promoting tumor growth; shaping the tumor microenvironment (i.e., promoting changes in the tumor microenvironment via immune cell recruitment or extracellular matrix remodeling); regulating metabolic functions of tumor cells or inducing immunogenic cell death (i.e., in the context of oncolytic virotherapy).

Unraveling the role of TLRs expressed by transformed cells on tumor biology will help define therapeutic approaches against cancer beyond the proposed use of TLR agonists as activators of immune cells for immunotherapeutic interventions.

This Research Topic accepts Original Research, Systematic Review, Methods, Review and Mini-Review, Perspective, Case Report, Brief Research Report, Data Report. We welcome manuscripts focusing on, but not limited to, the following sub-topics:
• Role of Toll-like receptors expressed by transformed cells on tumor progression.
• Role of Toll-like receptors expressed by transformed cells on cell metabolism.
• Toll-like receptor ligands as inducers of immunogenic cell death, including activation via oncolytic therapies.
• Toll-like receptors expressed by transformed cells as targets for cancer therapeutics.
• Role of Toll-like receptors expressed by transformed cells in shaping the tumor microenvironment (immune cell infiltration, extracellular matrix remodeling)
• Signaling pathways activated by TLR agonists in cancer cells.
• Toll-like receptors in cancer drug resistance.

Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation are considered out of scope of this section.

Topic editor Dr. Kelly McCall is a founding member of the AOHBio Corporation. All other Topic Editors declare no competing interests with regards to the Research Topic subject.

Keywords: toll-like receptors, TLR, tumor microenvironment, TME, Immunogenic cell death, TLR activation, tumor metabolism, signaling pathways, tumor extracellular matrix


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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