Researchers from VIB and KU Leuven, together with colleagues from the University of California and the Swiss Institute for Experimental Cancer Research have demonstrated that, anti-angiogenic therapy can improve immune boosting treatments. The combination of these two therapies result in the growth of specialized vessels that deliver cancer-fighting immune cells to the tumor, potentially leading to more effective treatments and longer survival periods. The study results are published in the peer-reviewed Journal Science Translational medicine.
Angiogenesis- the growth of new blood vessels and suppression of the immune system – hallmarks of cancer, lot of evidences suggest that these two activities are interrelated. Treatments that prevent tumor blood vessel growth are effective only in a subset of patients. Similarly, the recent successes to directly stimulate the immune system with inhibitors of negative immune checkpoint regulators-such as antibodies against programmed cell death protein 1 (PD-1) or its ligand PD-1 has led to many clinical trials. However, only a minority of treated patients responded to immunotherapies, stressing the need to identify strategies that will increase response rate in patients.
Researchers provide evidence that anti-PD-L1 therapy can sensitize and prolong efficacy of anti-angiogenic therapy and conversely, anti-angiogenic therapy can improve anti PD-L1 treatment specifically when intratumoral HEV’s are generated that facilitate enhanced cell infiltration, activity and tumor cell destruction.
Blood Vessels help regulate immunity:
Tumors maintain an immunosuppressive environment by changing the characters of immune and vascular system to avoid being attacked by host’s immune systems. Increased blood supply and low immune activity are necessary for malignant cells to multiply.
The cancer cells can evade the host’s immune system by preventing the infiltration of white blood cells. The network of blood vessels itself is an important regulator of immunity because it controls WBC’s traffic.
The combination of immune system activating, and anti-angiogenic antibodies causes a positive feedback loop. The resultant growth of specific blood vessels that deliver cancer-fighting immune cells into the tumor. These HEVs (High endothelial venules) are normally found in lymphoid organs such as lymph nodes, where they transport WBCs.
The results of the study indicate that the 2 therapies stimulated significant growth of HEVs in pancreatic and mammary tumors, leading to malignant cells death and tumor shrinkage. The next step in this research involves investigating how intratumoral HEVs are formed and maintained.