Table 2.
Immunotherapy implications in obese cancer patients.
| Cell type | Reported findings on treatment implications in obese cancer patients | References |
|---|---|---|
| T cells |
PD-1/PD-L1 checkpoint inhibition Increased TILs, CD8+/CD4+ ratio, and improved response and survival. No irAEs observed. CAR T-cell therapy Impaired activity and proliferation of CAR T-cells by TGF-β, indicating potential benefit of combination treatment with TGF-β antagonists, in addition to PD-1/PD-L1 checkpoint inhibition. |
(29, 32, 97, 99) |
| γδ T cells |
γδ adoptive immunotherapy or Vγ9Vδ2 agonists Low efficacy in breast cancer due to γδ T cell exhaustion and plasticity. Potential detrimental effects due to induction of immunosuppressive γδ T cells by obese microenvironmental cues. |
(38, 40) |
| NK cells |
PD-1/PD-L1 checkpoint blockade Reduction in tumor burden. Adoptive iNKT cell therapy and IL-6Ra+ NK cell ablation Reduction in obesity, hyperlipidemia and leptin production, and upregulation of anti-inflammatory cytokines. Potential improved treatment response when combining checkpoint blockade with adoptive NK cell therapy. |
(55–57) |
| DCs |
DC-based immunotherapy Reduced efficacy in obese renal carcinoma model, associated with increased regulatory DCs and decreased CD8+ T cells. Potential improved response on combining DC-based immunotherapy with obesity interventions. |
(61, 63) |
| Macrophages |
TAM-specific depletion (M2pep, anti-MARCO) or reprogramming (epigenetic modulators) Improved treatment response (pre-clinical) in combination with checkpoint blockade (anti-PD-1/PD-L1, anti-CTLA4). |
(68–70, 72) |
| MDSCs |
LXRβ agonists (GW3965, RGX-104a) Induction of MDSC apoptosis and improved anti-tumor response (pre-clinical) in combination with checkpoint blockade. RGX-104 is in clinical trial for solid tumors as a single agent and in combination with PD-1 inhibitor (NCT02922764). |
(90) |
CAR, chimeric antigen receptor; CTLA-4, cytotoxic T lymphocyte-associated antigen 4; DC, dendritic cells; iNKT, invariant NK T cell; irAEs, immune related adverse events; MDSC, myeloid-derived suppressor cells; NK, natural killer cells; PD-1, programmed death-1; PD-L1, programmed death ligand 1; TILs, tumor infiltrating lymphocytes.