Part 2. Please read the following article and answer the following questions Isource: Modified fromNature 588, 693-698(2020) ]Despite its success in achieving the long-term survival of 10-30% of treated individuals, immune therapy is still inefiective formost patients with cancer. Many efforts are therefore underway to identify new approaches that enhance such immune checkpoint"therapy. Here we show that inhibiting PCSK9--a key protein in the regulation of cholesterol metabolism--can boost the responseof tumors to immune checkpoint therapy. through a mechanism that is independent of PCSK9's cholesterol-regulating functions.Deleting the PCSK9 gene in mo ouse cancer cells substantially attenuates their growth in mice in a manner that depends on cytotoxicT cells. It also enhances the efficacy of immune therapy that is rargeted at the checkpoint protein PDI. Furthermore. clinicallyapproved PCSK9-neutralizing antibodies synergize with anti-PDI therapy in suppressing tumor groweh in mouse models of cancer.Inhibiting PCSK9 either through genetic deletion or using PCSK9 antibodies--increasts the expression of majorhistocompatibility protein class I (MHC I )proteins on the tumor cell surtace. promoting robust intratumoral infiltration of cytotoxicT cells. Mechanistically. we find that PCSK9 can disrupt the recyeling of MHC I to the cell surface by associating with it physicallyand promoting its relocation and degradation in the lysosome. Together. these results suggest that inhibiting PCSK9 is a promisingway to enhance immune checkpoint therapy for cancer.
【題組】5. PCSK9 modulates immune checkpoint therapy through regulating cholesterol level. (3%)
(A) True
(B) False
(C) Not mentioned in the article