💉 Reactivating immunity against cancer

Hypoxia, or local lack of oxygen, which develops in aggressive cancer tumors is one of the main obstacles to the effectiveness of immunotherapies. It profoundly alters the function of immune cells while promoting the survival of cancer cells.

Scientists have managed to counteract this phenomenon by developing an innovative biomaterial capable of delivering oxygen within the tumor and restoring the antitumor activity of immune cells. These results, published in the journal Cell Biomaterials, open new perspectives in oncology.


For many cancers that develop through the growth of solid tumors, hypoxia, or lack of oxygen in tissues, is a major hindrance to the action of immune cells. It occurs when the rapid growth of cancer cells exceeds the tissue's ability to form new blood vessels. Some regions then become very poor in oxygen, which profoundly disrupts the functioning of the immune system and limits the effectiveness of many immunotherapies.

Among the cells most affected by this lack of oxygen are dendritic cells. These sentinels of the immune system detect tumor antigens and activate T lymphocytes responsible for destroying cancer cells. In a hypoxic environment, their ability to capture antigens, migrate to lymph nodes, and trigger an effective immune response is strongly impaired. Moreover, they are not only immunosuppressed: they can also acquire a tolerogenic and protumoral phenotype, thus contributing to immune escape.

Cancer cells, on the other hand, easily adapt to this lack of oxygen and are therefore not weakened by this phenomenon, which is both a consequence of the rapid growth of the tumor and a shield that it exploits, particularly to neutralize immune cells.

To counteract this phenomenon, a Franco-American team from the Polymers, Biopolymers, Surfaces laboratory (CNRS/University of Rouen Normandy) and Northeastern University (Boston), has developed injectable polymer biomaterials called O₂-cryogels. These macroporous structures, composed notably of hyaluronic acid, are comparable to soft and elastic sponges loaded with calcium peroxide (CaO₂).

Highly deformable and compressible, they can be directly injected with a syringe into tumor tissues in a non-invasive manner. They regain their shape after injection and gradually release oxygen through the hydrolysis of calcium peroxide upon contact with tissue water.

This oxygenation of the tumor microenvironment allows the restoration of immune cell activity. Dendritic cells regain their antitumor capacity, particularly to capture tumor antigens, migrate to lymph nodes, and activate T lymphocytes. Cytotoxic T lymphocytes proliferate more, and the destruction of tumor cells is significantly enhanced. By reestablishing an active immune environment, this strategy could transform some so-called "cold" tumors, poorly infiltrated by immune cells, into "hot" tumors, more likely to respond to immunotherapies.

Beyond this proof of concept published in the journal Cell Biomaterials, these biomaterials could become a versatile therapeutic platform to enhance the effectiveness of many existing immunotherapy strategies, such as anticancer vaccines or cellular therapies currently under investigation.

Editor: Anne-Valerie FOILLARD RUZETTE