The expanding landscape of inflammatory cells affecting cancer therapy

Abstract

Tumour-infiltrating myeloid cells (TIMCs) are critical regulators of cancer growth. The different phenotypes, functions and therapeutic effects of these phagocytes have, however, been difficult to study. With the advent of single-cell-based technologies, a new 'worldview' is emerging: the classification of TIMCs into subtypes that are conserved across patients and across species. As the landscape of TIMCs is beginning to be understood, it opens up questions about the function of each TIMC subtype and its drugability. In this Perspective, we outline the current map of TIMC populations in cancer and their known and presumed functions, and discuss their therapeutic implications and the biological research questions that they give rise to. The answers should be particularly relevant for bioengineers, materials scientists and the chemical and pharmaceutical communities developing the next generation of cancer therapies.

Fig. 1 ∣. Tumour-infiltrating myeloid cell types.

a, Two-dimensional visualization of immune and non-immune single-cell transcriptomes in lung tumours from patients. The data are shown using SPRING, a pipeline for data filtering, normalization and visualization using force-directed layouts. Each dot represents a single cell. b, SPRING plots of TIMC subsets from the same patients. c, Identification of expression-enriched genes in each TIMC subset, as compared with all others in the microenvironment of the human lung tumour. TPM: gene transcripts per million; TPMREF, second-highest expression value per gene transcripts per million (for details, see ref. ). d, Classification of macrophage subsets by M0-like, M1-like and M2-like gene signatures. Figure adapted with permission from ref. .

Fig. 2 ∣. Five therapeutic opportunities relevant to TIMC populations.

Better understanding the TIMC landscape can help discover new therapeutic targets (yellow), pharmacologically manipulate phagocytosis (blue), improve the delivery of drugs (orange), ablate or prevent the recruitment of pro-tumoral TIMC subsets (green) and unleash antitumoral TIMC responses (purple).