• colon carcinogenesis
• cancer immunobiology
• mucosal immunology
• gastrointestinal cancer

We read with great interest the paper by de Vries et al 1 which provides an interesting and unbiased characterisation of the immune contexture of colorectal cancer (CRC), the third most common cancer worldwide.2 By mass cytometric analysis together with single cell RNA sequencing, the authors identified several clusters of immune cells infiltrating CRC. They show that natural killer (NK) cells (identified as CD127⁻CD56⁺CD45RO⁺) are the prevalent innate lymphoid cell (ILC) population. NK cells are cytotoxic cells and can be distinguished from the non-cytotoxic CD127⁺ ‘helper’ ILC subsets (hILCs), which are specialised in the secretion of different sets of cytokines.3 Because of the low numbers of CD127⁺ hILCs, the authors did not characterise further hILC subsets. However, given their capacity to rapidly respond to environmental signals and pathogenic challenges, hILCs serve as important sentinels of mucosal tissue homeostasis.4 Therefore, their possible role both in CRC pathogenesis and in antitumour response has yet to be determined. Data on the ILC subset composition in CRC may allow improvement in therapeutic strategies for the control of this tumour by either suppressing or harnessing ILC function.

In this context, we analysed ILC subsets in samples from 33 resected primary CRC (online supplementary table 1) in comparison with matched normal mucosa (from the same patient), sampled 10 cm distant from the tumour (see …