HS3ST1 and neoplasm: • ILC1s express inhibitory receptors and undergo inhibitory functional turnover in late CRC.• ILC2-C can promote tumor progression. HS3ST1 and PD1 are highly expressed in ILC2 in advanced CRC tumors, and lack of HS3ST1 or PD1 in ILC2s inhibited tumor growth.• ILC3s transdifferentiate into ILCregs during CRC progression, and ILCregs promotes tumor growth.