Twenty-One Flavors of Type 1 Innate Lymphoid Cells with PD-1 (Programmed Cell Death-1 Receptor) Sprinkles

Abstract

Innate lymphoid cells (ILCs) are tissue-resident immune cells that have been recently implicated in initiating and driving anti-tumor responses. ILCs are classified into three main groups, namely type 1 ILCs (ILC1), type 2 ILCs, and type 3 ILCs. All three groups have been implicated in either eliciting pro or anti-tumor immune responses in different cancer subtypes with the consensus that ILCs cannot be overlooked within the field of anti-tumor immune responses. In this review, we will specifically expand on the knowledge on ILC1, their characterization, function, and plasticity in anti-cancer immune responses. Within this premise, we will discuss caveats of ILC1 characterization, and expand on the expression and function of immune checkpoint receptors within ILC1 subsets, specifically focusing on the role of programmed cell death-1 receptor in controlling specific ILC1 responses. We summarize that ILC1s are a vital component in initiating anti-tumor responses and can be boosted by checkpoint receptors.

Keywords: EOMES; ILC1; LAG3; PD-1; T-bet; TIGIT.

Graphical Abstract

Figure 1:

The variation in cell marker and transcription factor expression in ILC1s in mice (left panel) and humans (right panel). ? denotes conflicting data on marker expression in ILC1s. A variety of co-receptors are upregulated in the TME. Abbreviations: ILC1, innate-lymphoid cell 1; ILC1l, type 1 innate-like ILC1; ieILC1, intraepithelial ILC1. Refs [5, 6, 15, 21, 29, 31, 38, 40–43, 46, 51, 71].