Jean Hausser

Four tumor micro-environmental niches explain a continuum of
inter-patient variation in the macroscopic cellular composition of
breast tumors.

Jean Hausser

Karolinska Institutet

The tumor microenvironment is a complex, self-organising tissue whose
architecture determines prognostic and response to therapy. There is
significant variation in the cellular and spatial architecture of the
tumor-microenvironment within and across patients. Are there rules that
constrain the architecture of the tumor-microenvironment? To find out,
we develop a quantitative framework of tumor architecture inspired by
ideas from satellite imaging, which we apply on deep single-cell
profiling and multiplex imaging data in breast tumors. Data analysis
shows that inter-patient variation in the macroscopic cellular
composition of tumors is structured as a continuum explained by four
tumor niches. These niches have their origin in tumor micro-architecture
and are shared across patients and tumor subtypes. Niche prevalence
depends strongly on the patient, which constraints and explains
inter-patient variation. The present framework facilitates interpreting
inter-patient variation in terms of a tractable number of
micro-environmental niches which serve as organizational entities at the
meso-scale to bridge the micro- and macro- scales of tumor architecture.