SPP1 and kidney cancer: In addition, expressions of signature genes for triggering receptor expressed on myeloid cells 2 (TREM2)-high TAMs which are associated with poor prognosis, including secreted phosphoprotein 1 (SPP1) that acts as an immune checkpoint to suppress T cell function, were enriched in HLRCC-associated kidney cancer, further suggesting that suppressed TAMs in HLRCC-associated kidney cancer may give rise to immune tolerance (Figure 3J) (Hu et al., 2020; Klement et al., 2018; Molgora et al., 2020; Xiong et al., 2020).