| First Author | Badrinath S | Year | 2022 |
| Journal | Nature | Volume | 606 |
| Issue | 7916 | Pages | 992-998 |
| PubMed ID | 35614223 | Mgi Jnum | J:345021 |
| Mgi Id | MGI:7367069 | Doi | 10.1038/s41586-022-04772-4 |
| Citation | Badrinath S, et al. (2022) A vaccine targeting resistant tumours by dual T cell plus NK cell attack. Nature 606(7916):992-998 |
| abstractText | Most cancer vaccines target peptide antigens, necessitating personalization owing to the vast inter-individual diversity in major histocompatibility complex (MHC) molecules that present peptides to T cells. Furthermore, tumours frequently escape T cell-mediated immunity through mechanisms that interfere with peptide presentation(1). Here we report a cancer vaccine that induces a coordinated attack by diverse T cell and natural killer (NK) cell populations. The vaccine targets the MICA and MICB (MICA/B) stress proteins expressed by many human cancers as a result of DNA damage(2). MICA/B serve as ligands for the activating NKG2D receptor on T cells and NK cells, but tumours evade immune recognition by proteolytic MICA/B cleavage(3,4). Vaccine-induced antibodies increase the density of MICA/B proteins on the surface of tumour cells by inhibiting proteolytic shedding, enhance presentation of tumour antigens by dendritic cells to T cells and augment the cytotoxic function of NK cells. Notably, this vaccine maintains efficacy against MHC class I-deficient tumours resistant to cytotoxic T cells through the coordinated action of NK cells and CD4(+) T cells. The vaccine is also efficacious in a clinically important setting: immunization following surgical removal of primary, highly metastatic tumours inhibits the later outgrowth of metastases. This vaccine design enables protective immunity even against tumours with common escape mutations. |
