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Editorial
. 2018 Mar;10(3):1294-1299.
doi: 10.21037/jtd.2018.03.62.

Combination immuno-oncology therapy with immune checkpoint blockers targeting PD-L1, PD-1 or CTLA4 and epigenetic drugs targeting MYC and immune evasion for precision medicine

Masaru Katoh  1
Affiliations
Editorial

Combination immuno-oncology therapy with immune checkpoint blockers targeting PD-L1, PD-1 or CTLA4 and epigenetic drugs targeting MYC and immune evasion for precision medicine

Masaru Katoh. J Thorac Dis. 2018 Mar.
No abstract available

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Conflict of interest statement

Conflicts of Interest: The author has no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Multi-stage carcinogenesis, genomics testing and targeted cancer therapy. Genetic predisposition (germline alterations), chronic infection and life style, such as alcohol drinking and tobacco smoking, are involved in progression to pre-malignant stages of carcinogenesis, whereas epigenetic dysregulation, genetic alterations (germline and somatic) and immune evasion are involved in progression to more advanced stages of carcinogenesis. Chemotherapy, radiotherapy and surgical operation are conventional cancer therapies. By contrast, epigenetic drugs, immuno-oncology drugs and receptor tyrosine kinase (RTK) inhibitors or anti-RTK monoclonal antibodies (mAbs) have emerged as promising targeted cancer therapies. Cancer gene panels detecting alterations in approximately 300 common cancer-related genes and whole genome sequencing comprehensively detecting alterations in common and rare cancer-related genes are next-generation sequencing (NGS)-based genomics testing. Genomics testing is necessary to select patients and time points for targeted therapy.
Figure 2
Figure 2
Strategies targeting immune evasion for cancer therapy. Immune evasion is defined as a defect in anti-tumor immunity in the tumor microenvironment. PD-1, CTLA4, LAG3 and TIM3 are immunosuppressive receptors that repress anti-tumor immunity, whereas 4-1BB and OX40 are immunostimulatory receptors that enhance anti-tumor immunity. Epigenetic dysregulation (EpiG), metabolomic aberration (Metabo), myeloid-derived suppressor cells (MDSCs) and regulatory T (Treg) cells are also involved in immune evasion. By contrast, neoantigens (neo-Ag) derived from tumor cells and chimeric antigen receptor-modified T (CAR-T) cells elicit anti-tumor immunity. Immune molecules or cells promoting immune evasion are shown by red circle; epigenetic or metabolomic mechanisms promoting immune evasion are shown by yellow circle; and immune molecules or cells promoting anti-tumor immunity are shown by green circle. Antagonistic monoclonal antibodies (mAbs), CAR-T cells and small-molecule inhibitors shown in red are therapeutics targeting immune evasion. Agonistic mAbs and cancer vaccines shown in green are therapeutics enhancing anti-tumor immunity. Immune checkpoint blockers, including anti-PD-L1 mAbs (atezolizumab, avelumab and durvalumab), anti-PD-1 mAbs (nivolumab and pembrolizumab) and anti-CTLA4 mAb (ipilimumab), are representative immuno-oncology drugs approved for the treatment of cancer patients, whereas most of other immunomodulatory therapeutics are investigational drugs in clinical trials or preclinical research.
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References

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