Targeting CD47-mediated cancer senescence, a novel strategy for cancer immunotherapy

A transmembrane protein that is extensively expressed, CD47 has an important role in the senescence of cancer cells. Therapy-induced senescence (TIS) by chemotherapy and radiotherapy restrains tumor proliferation yet drives immune evasion and treatment resistance, where CD47 acts as a core regulatory molecule linking cellular senescence and tumor immune escape. In this mini-review, we summarize the mechanisms governing CD47 upregulation during TIS, ranging from DNA damage response signaling, metabolic reprogramming and epigenetic modulation to post-transcriptional RNA modification. After addressing how CD47 is upregulated in TIS, we summarized the function of CD47 in both the maintaining the senescent statue and preventing senescent escape. Three major pathways are addressed. TSP-1/CD47 axis functions as both senescence maintenance and preventing escape, while, p16/c-MYC/CD47 axis and CD47/QPCT axis are responsible for senescence maintenance. Moreover, we summarize the therapeutic strategies toward CD47 blockade as s senolytic way, pointing out a novel strategy for oncotherapy. Overall, CD47 is a pivotal molecular bridge between TIS and immune tolerance. Future research on the role CD47 of cancer senescence, especially after chemotherapy or radiotherapy, could provide novel insight for oncotherapy.