TABLE 1.
Immunomodulatory effects of antiangiogenic treatments in preclinical and translational studies
| Antiangiogenic treatment | Cancer type | Key result | Reference |
|---|---|---|---|
| VEGF studies | |||
| Bevacizumab or sorafenib | NA |
Dendritic cell differentiation↑ HLA‐DR and CD86 expression↑ |
[31] |
| Bevacizumab | Renal cell carcinoma (Caki‐1) in nude mice | Circulating VEGFR1+ myeloid cells↓ | [67] |
| Bevacizumab | Multiple tumors in human patients |
Immature dendritic cells in peripheral blood↓ Dendritic cell population↑ Allostimulatory capacity of dendritic cells↑ T cell proliferation↑ |
[44] |
| VEGF‐specific antibody (clone G6‐31) + aspirin |
Ovarian cancer (ID8‐VEGF) Colon cancer (CT26) Renal cell cancer (Renca) Melanoma (B16) |
Influx of tumor‐rejecting CD8+ over FoxP3+ T cells↑ CD8‐dependent tumor growth suppression↑ |
[55] |
| Angiopoietin studies | |||
| AMG386 (Trebananib, an Ang‐1/2 neutralizing peptibody) | Glioblastoma (GL261) |
Number of F4/80+ macrophages↑ Microvessel coverage with desmin+ pericytes↑ |
[26] |
| MEDI3617 (an anti‐Ang‐2‐neutralizing antibody) + Cediranib | Glioblastoma (Gl261) | Reprogramming TAMs towards the M1 polarized subtype | [27] |
| A2V (Ang‐2/VEGF bispecific antibody) | Glioblastoma (GL261) | Reprogramming TAMs towards the M1 polarized subtype | [28] |
| A2V (Ang‐2/VEGF bispecific antibody) | Melanoma (B16‐OVA) |
Proportions of CTLs expressing an IFNγ+ or CD69+ phenotype↑ Proportion of intratumoral, OVA‐specific CTLs↑ Proportion of APCs that cross‐presented the OVA‐derived peptide↑ Phagocytic activity of APCs↑ |
[29] |
| AMG386 + MET kinase inhibitor | Clear cell renal cell carcinoma (RP‐R‐02LM) | The presence of TAMs in the tumor microenvironment↓ | [30] |
Abbreviations: Ang, angiopoietin; APC, antigen‐presenting cell; CTL, cytotoxic T lymphocyte; NA, not applicable; TAM, tumor‐associated macrophage; IFN, interferon; VEGF, vascular endothelial growth factor.