Researchers have discovered that low oxygen levels in tumors may actually boost certain immune responses against cancer, contrasting with the common belief that hypoxia solely aids cancer development. Their study has pinpointed a specific group of macrophages that show a stronger immune reaction in low-oxygen environments within tumors.
Researchers from the Epigenetics and Immune Disease lab at the Josep Carreras Leukaemia Research Institute have discovered that low oxygen levels in tumors might enhance some immune responses against cancer, challenging the prevailing view that hypoxia only aids cancer growth. Their research has uncovered a distinct group of macrophages exhibiting stronger immune reactions under conditions of low oxygen present in tumors.
Cancer creates a complex environment, where tumors often establish a microenvironment that is characterized by low oxygen levels, referred to as hypoxia. This occurs as tumors grow quickly, outpacing their blood supply due to an inefficient vascular network. The resulting oxygen-deficient atmosphere compels both tumor cells and nearby tissues to adapt in ways that generally support tumor survival and expansion.
This adaptation also affects the immune cells in the tumor microenvironment, which are often conditioned by cancer cells to tolerate them and sometimes even assist in tumor growth, neglecting their primary role. Consequently, hypoxia is frequently linked to more aggressive cancers and unfavorable patient outcomes, as it drives changes that enhance tumor resistance to treatments.
However, this established notion is not absolute. Recently, Dr. Esteban Ballestar’s team at the Josep Carreras Institute published findings in the journal Science Advances, outlining the identification and characterization of an immune cell population that becomes more effective against cancer cells in hypoxic conditions. This immune cell group shows specific epigenetic changes and involvement of particular factors that attribute to their enhanced functionality.
This unexpected finding enriches our comprehension of how hypoxia impacts cancer. While it is commonly associated with promoting cancer progression, this new research indicates that a portion of the immune system can actively combat cancer. The study specifically focused on macrophages, crucial immune cells that play roles in maintaining tissue health and fighting infections.
Typically, in the tumor microenvironment, macrophages are reprogrammed to inhibit immune activity, leading to poorer patient outcomes. However, this research indicated that some macrophages may undergo marked changes under hypoxia that actually boost their ability to initiate an immune response against tumors.
In particular, researchers identified a set of inflammation-related genes that become more active in macrophages exposed to hypoxia, influenced by notable regulatory molecules like NF-κB and HIF1α. In cases of bladder and ovarian cancers, tumors containing these hypoxic macrophages that enhance inflammation corresponded with improved patient outcomes.
This research challenges the long-held belief that low oxygen levels in tumors only contribute to cancer advancement. Instead, it points to a potential new approach in harnessing the body’s immune system to more effectively battle cancer.
This study, with first authors Carlos de la Calle-Fabregat and Jose Calafell-Segura, was conducted in collaboration with Dr. Florent Ginhoux from the Gustave Roussy Cancer Center in Paris, Dr. Ángel Corbí from the Centro Superior de Investigaciones Biológicas, CSIC in Madrid, and Dr. Cristina Muñoz-Pinedo from the Institut d’Investigació Biomèdica de Bellvitge (IDIBELL). The research received funding from the Spanish Ministry of Science, Innovation and Universities.
