Journal
CANCER MEDICINE
Volume -, Issue -, Pages -Publisher
WILEY
DOI: 10.1002/cam4.5696
Keywords
angiogenesis inhibitors; immune checkpoint inhibitors; immunotherapy; lung neoplasms; tumor microenvironment
Categories
Ask authors/readers for more resources
In lung cancer, immune checkpoint inhibitors (ICIs) alone are not sufficient for inhibiting tumor growth. Angiogenic inhibitors (AIs) are needed to normalize tumor blood vessels for better immune cell infiltration. This study examined the effects of pre-administering an AI for lung cancer immunotherapy in a mouse model. Pre-administration of the AI improved immune cell infiltration and enhanced the therapeutic effects of ICIs.
In lung cancer, immune checkpoint inhibitors (ICIs) are often inadequate for tumor growth inhibition. Angiogenic inhibitors (AIs) are required to normalize tumor vasculature for improved immune cell infiltration. However, in clinical practice, ICIs and cytotoxic antineoplastic agents are simultaneously administered with an AI when tumor vessels are abnormal. Therefore, we examined the effects of pre-administering an AI for lung cancer immunotherapy in a mouse lung cancer model. Using DC101, an anti-vascular endothelial growth factor receptor 2 (VEGFR2) monoclonal antibody, a murine subcutaneous Lewis lung cancer (LLC) model was used to determine the timing of vascular normalization. Microvessel density (MVD), pericyte coverage, tissue hypoxia, and CD8-positive cell infiltration were analyzed. The effects of an ICI and paclitaxel after DC101 pre-administration were investigated. On Day 3, increased pericyte coverage and alleviated tumor hypoxia represented the highest vascular normalization. CD8+ T-cell infiltration was also highest on Day 3. When combined with an ICI, DC101 pre-administration significantly reduced PD-L1 expression. When combined with an ICI and paclitaxel, only DC101 pre-administration significantly inhibited tumor growth, but simultaneous administration did not. AI pre-administration, and not simultaneous administration, may increase the therapeutic effects of ICIs due to improved immune cell infiltration.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available