Table 1.

Phenotypes and functions of ILCs in bladder cancer.

ILC subset	Cytokines produced	Activating cytokines	Transcription factors	Role in bladder cancer
NK cells	IFNγ, perforin, granzyme B, TNFα	IL12, IL15, IL18	T-bet, Eomesodermin (Eomes)	Dysfunctional NK cells with low expression of CD56 and activation markers accumulate in high-stage bladder tumors, suggesting the loss of NK cell-mediated protective functions.
ILC1	IFNγ	IL12, IL15	T-bet	ILC1s exhibit an exhausted phenotype, characterized by decreased cytotoxicity and increased exhaustion markers.
ILC2	IL4, IL5, IL9, IL13	IL25, IL33, TSLP	GATA-3, RORα	ILC2 secrete IL13 in the TME favoring the polarization of M2 macrophages and M-MDSCs.
ILC3	CXCL10, IL22, IL17, GM-CSF	IL23, IL1β	RORγt, T-bet, AHR	ILC3s coexpress CD103 and CD69, markers of tissue-resident innate memory cells. ILC3s share significant phenotypic features with ILC1s suggesting potential plasticity and overlapping functions of these ILCs in bladder tumors.

Abbreviations: T-bet, T-box transcription factor TBX21; GATA3, GATA binding protein 3; TSLP, Thymic stromal lymphopoietin; Areg, Amphiregulin; CXCL10, C-X-C motif chemokine ligand 10.