Abrogation of SAP expression from AITL-like tumors leads to tumor regression. (A) Increased expression of the SLAM adaptor protein, SAP in CD4 cells from AITL-like tumors (n = 5 tumor-free; n = 8 nontumorous [non-tumor]; and n = 12 tumorous [tumor] samples). (B) Frequency and MFI of SAP in CXCR5⁺PD-1⁺ cells from tumor-free, nontumorous, and tumor samples (n = 5 tumor-free; n = 8 nontumorous; and n = 12 tumorous samples). (C) SAP^hi CD4 cells from tumors are more proliferative, as depicted through increased frequencies of Ki-67⁺ cells (n = 4 tumor-free; n = 7 nontumorous; and n = 11 tumorous samples). (D) SAP^hi CD4⁺ tumor cells are more proliferative than SAP^lo as shown in representative histogram and frequencies. (E) Roquin^san/+ mice were bred with a CD4 specific tamoxifen-inducible Cre recombinase and conditional Sh2d1a allele (Roquin^san/+; Cd4-Cre^ERT2+/−; Sh2d1a^{f/y or f/f}). Representative time course (F) and sonograms (G) demonstrating tumor regression in mice with CD4-specific abrogation of SAP (n = 5 Roquin^san/+; Cd4-Cre^ERT2+/−; Sh2d1a^+/+; n = 9 Roquin^san/+; Cd4-Cre^ERT2+/−; Sh2d1a^{f/y or f/f}). In panel F, we reused CD4-CreERT2 control data shown in Figure 2I to perform statistical analysis for different time points. Error bars in panels A-D,F represent the SEM. Data are pooled from at least 2 independent experiments. *P < .05; **P < .01; ***P < .001; ****P < .0001.