Table 3 Combining lipid-targeted therapies with immunotherapy
From: Lipid metabolic reprogramming in tumor microenvironment: from mechanisms to therapeutics
Target | Treatment | Phase | Tumor type | Effects on immune cells | Combined treatment | Reference |
|---|---|---|---|---|---|---|
CD36 | JC63.1 (Anti-CD36) | In vivo | B16 melanoma lung metastatic model | Reduced ferroptosis and enhanced anti-tumor function in CD8+ T cells | Anti-PD-1 Ab | [169] |
In vivo | YUMM1.7 melanoma-bearing mice model | Reduced accumulation and promoted apoptosis in Treg cells Increased accumulation in CD8+ TILs | Anti-PD-1 Ab | [8] | ||
SSO | In vivo | HCC murine models | Decreased Tregs and MDSCs Increased IFN-γ+ and granzyme B+ CD8+ T cells | Anti-PD-1 Ab | [153] | |
FATP2 | Lipofermata | In vivo | TC-1 and LLC tumor-bearing mice model | Promoted anti-tumor effect of CD8+ TILs | Anti-CTLA4 Ab | [10] |
In vivo | B16 melanoma and LLC tumor-bearing mice model | Activated T cells and inhibited suppressive role of MDSCs | Anti-PD-L1 Ab | [221] | ||
FASN | C75 | In vitro | TAMs coculture with TPC-1 thyroid tumor | Reduced extracellular cytokine levels from TAMs through inhibition of lipid biosynthesis | NA | [191] |
CPT | Etomoxir | In vitro | TAMs coculture with various tumor cell lines | Suppressed pro-tumor function of TAMs through inhibition of FAO | NA | [187] |
In vivo | Lewis lung and MC38 colon tumor-bearing mice | Increased number of adoptively transferred OT-1 T cells infiltrating the tumors and cells producing IFN-γ | ACT | [222] | ||
In vivo | GL261 glioblastoma-bearing mice model | Boost TAM phagocytosis and anti-tumor effect | Anti-CD47 Ab | [312] | ||
PPAR | Bezafibrate (PGC-1α/PPAR agonist) | In vivo | MC38 colon tumor-bearing mice | Enhanced proliferation during the early phase and inhibited apoptosis of the effector T cells | Anti-PD-1 Ab | [164] |
In vivo | Lewis lung tumor-bearing mice | Maintained survival and functional capacity of CD8+ TILs | Anti-PD-L1 Ab | [313] | ||
GW501516 (PPAR agonist) | In vivo | B16 melanoma-bearing mice | Activated the expression of T-bet and IFN-γ level in CD8+ T cells | ACT | [314] | |
Rosiglitazone (PPARγ inhibitor) | Phase II | Solid Tumor Malignancies | NA | Nivolumab, Pembrolizumab | NCT04114136 | |
TPST-1120 (PPARα inhibitor) | Phase I | Advanced Cancers | NA | Nivolumab | NCT03829436 | |
HMGCR | Statin | In vivo | MOC1 oral tumor-bearing mice | Activated effector T cells Shifted macrophages from M2 to M1 | Anti-PD-1 Ab | [315] |
Prospective cohort | Pleural mesothelioma, NSCLC | NA | Nivolumab | [311] | ||
Retrospective study | NSCLC | NA | Nivolumab, Pembrolizumab | [316] | ||
Prospective cohort | NSCLC | NA | PD-1/PD-L1 inhibitors | NCT05636592 | ||
PSK9 | Evolocumab | In vivo | MC38 colon tumor-bearing mice | Boost the number of active IFN-γ+ CTLs | Anti-PD-1 Ab | [317] |
ACAT | Avasimibe | In vivo | B16 melanoma and lung tumor-bearing mice | Enhanced anti-tumor effect and cytokine production of CD8+ T cells | Anti-PD-L1 Ab | [172] |
In vivo | B16 melanoma-bearing mice | Increased tumor cell apoptosis and T cell effect | ACT | [303] | ||
| Â | Â | Tissue | HCC | Enhanced expansion of cytolytic and non-cytolytic antigen-specific CD8+ T cells | Nivolumab | [318] |
COX | Asprin | Phase II | MSI-H colorectal cancer | NA | Anti-PD-1 Ab | NCT03638297 |