Lung cancer-induced alterations in the bone marrow progenitor and monocyte compartment with implications for tumor-associated and healthy tissue macrophages

Tumor-associated macrophages (TAMs) are considered as next-generation
therapeutic targets in cancer, considering their multiple tumor-promoting
functions. TAMs are often derived from classical monocytes, which
differentiate into a variety of transcriptionally and functionally different TAM
subsets. However, it is unknown whether ontogenically distinct classical
monocyte subsets (derived from GMP or MDP progenitors) contribute to
TAM formation, nor is it clear whether these monocytes are epigenomically
and functionally imprinted by a tumor long before they reach the tumor site.
Here, we will employ non-small cell lung carcinoma models, innovative
mouse strains and single cell technologies to assess whether a remote
tumor is able to alter the ontogeny of classical monocytes and whether
distinct monocytes differentially contribute to TAM formation. Moreover, we
will scrutinize the tumor-induced transcriptomic and epigenomic alterations
in these classical monocytes and their progenitors and will assess whether
these affect monocyte functionality and differentiation potential, even in nondiseased organs.