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. Author manuscript; available in PMC: 2023 Nov 14.
Published in final edited form as: Cancer Cell. 2022 Nov 3;40(11):1324–1340.e8. doi: 10.1016/j.ccell.2022.10.012

Figure 7. The proposed model of SIRPα-mediated T-cell-centric immunotherapy response.

Figure 7.

The proposed model consists of three consecutive layers, from the molecular mechanism to impacts on clinical outcomes. The left and right sides show the contrasting situations of SIRPA high expression vs. SIRPA low expression in tumor cells. On the left side, within tumor cells, SIRPAP1 upregulates SIRPA by functioning as a competing endogenous RNA; within the tumor microenvironment (TME), SIRPα on the surface of tumor cells interacts with CD47 on CD8+ T cells to enhance cell-cell adhesion between these two cell types; and consequently, the enhanced cell-cell interaction increases the T cell killing effect, leading to a better response to anti-PD-1/PD-L1 therapy. In contrast, on the right side, tumor cells with low SIRPA expression have moderate cell-cell adhesion with CD8+ T cells, thereby rendering resistance to anti-PD-1/PD-L1 therapy. The bottom panels show clinical implications of the proposed model in terms of indication for treatment, immunotherapy biomarker, and therapeutic development.