Using single-cell transcriptomics, Qi and Crinier et al. investigated the heterogeneity of helper-like innate lymphoid cells (ILCs) from blood, normal mucosa, and tumor tissues from colorectal cancer (CRC), and identified the presence of tumor-specific ILC subsets. The normal gut mucosa contained ILC1s, ILC3s, and ILC3/NKs, but no ILC2s, whereas the tumor tissues from CRC patients contained tumor-specific ILC1-like and ILC2 subsets. Tumor-specific ILCs and blood ILCs from patients with CRC selectively expressed higher levels of SLAMF1, and high levels of SLAMF1 expression correlated with better survival in patients with CRC.

Contributed by Shishir Pant

ABSTRACT: Innate lymphoid cells (ILCs) are tissue-resident lymphocytes differing from conventional T lymphocytes in having no antigen-specific receptors. ILCs include natural killer (NK) cells, helper-like ILC1s, ILC2s, and ILC3s, and lymphoid tissue-inducer (LTi) cells. Tumor ILCs are frequently found in various cancers, but their roles in cancer immunity and immunotherapy remain largely unclear. We report here the single-cell characterization of blood and gut helper-like ILC subsets in healthy conditions and in colorectal cancer (CRC). The healthy gut contains ILC1s, ILC3s, and ILC3/NKs, but no ILC2s. Additional tumor-specific ILC1-like and ILC2 subsets were identified in CRC patients. Signaling lymphocytic activation molecule family member 1 (SLAMF1) was found to be selectively expressed on tumor-specific ILCs, and higher levels of SLAMF1+ ILCs were observed in the blood of CRC patients. The SLAMF1-high group of CRC patients had a significantly higher survival rate than the SLAMF1-low group, suggesting that SLAMF1 is an anti-tumor biomarker in CRC.

Author Info: (1) Shanghai Institute of Immunology, Department of Immunology and Microbiology, and the Ministry of Education Key Laboratory of Cell Deathand Differentiation, Shanghai Jiao Tong U

Author Info: (1) Shanghai Institute of Immunology, Department of Immunology and Microbiology, and the Ministry of Education Key Laboratory of Cell Deathand Differentiation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China (2) Shanghai Jiao Tong University School of Medicine-Yale Institute for Immune Metabolism, Shanghai Jiao Tong University School of Medicine,Shanghai 200025, China (3) Aix-Marseille Universite, CNRS, INSERM, Centre d’Immunologie de Marseille-Luminy, 13009 Marseille, France (4) Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China (5) Innate Pharma Research Laboratories, Innate Pharma, 13009 Marseille, France (6) Immunology, Marseille Immunopole, Hopital de la Timone, Assistance Publique des Hopitaux de 13005 Marseille, France (7) Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China (8) These authors contributed equally (9) Lead contact