LAUSR

Immunotherapy based on checkpoint blockade has revolutionised cancer treatment during last years. Whereas this approach fails in a relevant group of patients, the knowledge on tumour microenvironment (TME) opened the possibility to the use of additional therapeutic strategies to potentiate antitumour immunity, including depletion of protumourigenic or immune suppressive and activation of specific immune populations using agonistic antibodies. Nevertheless, due to the complexity of the TME, many of these strategies have been indiscriminately advanced to the clinic without clear mechanistic hypotheses. Nowadays, single-cell RNA sequencing (scRNA-seq)-based transcriptome analyses identify T cell heterogeneity, elucidating dynamic relationships between T cells and the complexity of tumour-infiltrating myeloid cells, including tumour associated macrophages (TAMs) and dendritic cells (DCs), which contribute to malignancy through production of tumour and angiogenic growth factors, extracellular matrix remodelling and immunosuppression.1 Multiple strategies to boost the function of DCs and TAMs have advanced to the clinic, with approaches to activate the CD40 and CSF1R receptor being widely explored. However, CSF1R inhibitors and CD40 agonists have shown limited monotherapy efficacy.2 In a brilliant investigation recently published in Cancer Cell, Zhang et al , presented the results obtained by using two scRNA-seq platforms to perform a high-resolution analysis of immune and stromal cell populations in tumours, adjacent normal tissues and blood from colorectal cancer (CRC) patients.3 The authors were able to reproduce a cell–cell interaction network to define key cell populations involved in regulating tumourigenesis and antitumour immunity and identified specific populations of TAMs and DCs as central nodes of cellular interaction evaluating these characteristics in preclinical models and human cancers. The authors demonstrated that two distinct TAM populations were present in CRC samples, consisting of C1QC+, involved in phagocytosis and antigen presentation, and SPP1+, implicated in angiogenesis. Neither of these populations fit the M1 and M2 dichotomous phenotypes. …