The lung cancer manages to “bring on its side” the macrophages by acting on their mothers even before they come out of the bone marrow.
The lung cancer is not limited to hiding from the immune system to spread without obstacles: it promises it to its advantage, dragging the macrophages – the “brush” cells on its side – even before mature, when they are in the bone marrow. The discovery published on Nature It provides more elements to combat lung cancer before it has completely passed off our white blood cells, and thus enhance immunotherapies.
Traitor macrophages
The success of immunotherapy for the treatment of non -small cell lung cancer (NSCLC), which represents 85% of cases of lung cancer, can be hindered by the protumoral macrophages – immune cells that instead of fighting the tumor, support it, favoring its diffusion. So far these cells have been thought to “convert” only once the tumor website, but the study led by the icihn school of medicine scientists of the Mount Sinai in New York, shows this process much earlier.
The macrophages are reprogrammed to assist the lung cancer well before they reach the respiratory organ: that is, when they are in the bone marrow and have yet to reach maturity. Thanks to advanced genomic mapping systems of the single cell, scientists have discovered that the tumor begins to influence the already behavior of the progenitor cells of the macrophages inside the bone marrow.
After this first blow, which directs the function of the macrophages even before they have differentiated, a second “hook” arrives well settled when the macrophages are located on the tumor website, which definitively certifies their conversion.
Early interventions
«If we wait to target and reprogram immune cells when they are inside the tumor, it could already be too late to reverse the process. We need strategies to intervene much earlier, while these cells are still in the development phase, so that they can prevent them from becoming an allied of cancer, “says Samarth Hegde, the first author of the study.
A possible target on which to intervene is a protein that helps cells to face stress, the NRF2. This protein appears changed on the progenitor cells of the macrophages co -opted by the tumor and definitively altered once the macrophages have become protmorial, on the site where cancer is present.
When the authors of the study tried to block the protein (through drugs or with genetic editing) in preclinical studies on mice and on humans, less proto -macrophages were formed and the immune system has managed to activate a more decisive response against the tumor.
Nrf2 protein inhibitors could make immunotherapies against this form of lung cancer more effective, according to the authors, who would also like to develop blood tests capable of identifying the precursors of the deviated macrophages, before they give rise to protuming macrophages. The next step will be to understand if these same genetic alterations are also present in other types of cancer.
