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Editorial
. 2020 Aug;8(16):1031.
doi: 10.21037/atm-20-1816.

Innate immune checkpoints for cancer immunotherapy: expanding the scope of non T cell targets

Luis F Campesato  1   2 , Chien-Huan Weng  1   2 , Taha Merghoub  1   2
Affiliations
Editorial

Innate immune checkpoints for cancer immunotherapy: expanding the scope of non T cell targets

Luis F Campesato et al. Ann Transl Med. 2020 Aug.
No abstract available

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-1816). The series “Tumor Associated Macrophages in Solid Tumor: Friend or Foe” was commissioned by the editorial office without any funding or sponsorship. TM reports other from IMVAQ therapeutics, personal fees from Immuno Therapeutics, personal fees from Pfizer, grants from Bristol-Myers Squibb, grants from Surface Oncology, grants from Kyn Therapeutics, grants and personal fees from Infinity Pharmaceuticals, Inc., grants from Peregrine Pharmeceuticals, Inc., grants from Adaptive Biotechnologies, grants from Leap Therapeutics, Inc., grants from Aprea, outside the submitted work; In addition, TM has a patent Inventor on patent applications related to work on Oncolytic Viral therapy issued, a patent Alpha Virus Based Vaccine issued, a patent Neo Antigen Modeling issued, a patent CD40 pending, a patent GITR issued, a patent OX40 issued, a patent PD-1 issued, and a patent CTLA-4 issued. The authors have no other conflicts of interest to declare.

Figures

Figure 1
Figure 1
Molecular targets to enhance innate immunity in cancer therapy. Left, inhibitory checkpoints on the surface (Siglec-10, SIRPα) or cytoplasm (PI3Kγ, IDO) of tumor-associated macrophages (TAMs) suppress their effector functions of phagocytosis and antigen-presentation to T-cells. To escape from immune surveillance, tumors cells evolve with multiple pathways including IDO-derived L-Kynurenine which mediates T-cell suppression and the overexpression of CD24 and/or CD47, which suppress phagocytosis by engaging to Siglec-10 and/or SIRPα expressed in macrophages. Proposed mechanisms regarding Siglec-10 in down modulation of TLR-signaling is still unclear. Right, blockade of CD47 and CD24 or stimulation of CD40 using mAbs and of IDO and PI3Kγ using small molecule inhibitors can potentiate the activation state of TAMs towards a pro-inflammatory antitumoral phenotype. Therapeutic strategies to enhance myeloid cell activation can result in increased adaptive immunity and tumor control and can be exploited in combination with other immunotherapies.
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References

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