Abstract: Prolonged exposure of CD8+ T cells to antigenic stimulation leads to a state of diminished function, termed exhaustion; during exhaustion there is a subset of functional CD8+ T cells defined by surface expression of SIRP(alpha) protein. On SIRP+ CD8+ T cells, expression of coinhibitmy receptors is counterbalanced by expression of co-stimulatory receptors and it is only these SIRP+ cells that actively proliferate, transcribe IFNg and show cytolytic activity. Therapeutic blockade of PD-L1 or other inhibitory receptors to reinvigorate exhausted CD8+ T cells expands the cytotoxic subset of SIRP+ CD8+ T cells.

Abstract: Methods and kits are provided for determining whether an individual is responsive to therapeutic CD47 blockade. Specifically, the disclosure provides methods of determining whether a cell or cell population is responsive to therapeutic CD47 blockade, the method comprising: assaying a cell sample from an individual to determine (a) the level of expression of signal regulatory protein alpha (SIRPalpha) on phagocytic immune cells, or (b) the genotype of the individual at a nucleotide polymorphism (SNP) associated with SIRPalpha expression. Further disclosed are SNPs associated with SIRPalpha expression.