Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges

By Dai Fukumura, Jonas Kloepper, Zohreh Amoozgar, D. Duda, Rakesh K. Jain. Nature Reviews Clinical Oncology, 2018

1,744 citations recorded by the source corpus.

Immunotherapy has emerged as a major therapeutic modality in oncology. Currently, however, the majority of patients with cancer do not derive benefit from these treatments. Vascular abnormalities are a hallmark of most solid tumours and facilitate immune evasion. These abnormalities stem from elevated levels of proangiogenic factors, such as VEGF and angiopoietin 2 (ANG2); judicious use of drugs targeting these molecules can improve therapeutic responsiveness, partially owing to normalization of the abnormal tumour vasculature that can, in turn, increase the infiltration of immune effector cells into tumours and convert the intrinsically immunosuppressive tumour microenvironment (TME) to an immunosupportive one. Immunotherapy relies on the accumulation and activity of immune effector cells within the TME, and immune responses and vascular normalization seem to be reciprocally regulated. Thus, combining antiangiogenic therapies and immunotherapies might increase the effectiveness of immunotherapy and diminish the risk of immune-related adverse effects. In this Perspective, we outline the roles of VEGF and ANG2 in tumour immune evasion and progression, and discuss the evidence indicating that antiangiogenic agents can normalize the TME. We also suggest ways that antiangiogenic agents can be combined with immune-checkpoint inhibitors to potentially improve patient outcomes, and highlight avenues of future research.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/f768a19ee78949540bebf9ae77628fd1f0f1f9c5

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. Daniel Chen
2. R. Apte
3. N. Ferrara
4. Rakesh K. Jain
5. A. Adamis
6. H. Gerber

In Molecular Biology

1. R. Apte
2. Daniel Chen
3. N. Ferrara
4. Rakesh K. Jain
5. A. Adamis
6. Peter Carmeliet
7. H. Gerber

In Oncology

1. Daniel Chen
2. R. Apte
3. N. Ferrara

Citations in the corpus

• VEGF in Signaling and Disease: Beyond Discovery and Development (2019, background): “As already pointed out, normalization has been associated with significantly lower doses of anti-VEGF antibodies (Fukumura et al., 2018).”
• Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma (2020, neutral): “Hypothyroidism 25 (25) 11 (11) 14 (14) 0 Palmar-plantar erythrodysesthesia syndrome 23 (23) 13 (13) 9 (9) 1 (1) Weight decreased 22 (22) 8 (8) 11 (11) 3 (3) Dysphonia 21 (21) 19 (19) 1 (1) 1 (1)”