We are pleased to announce the 2022 ISV Paper of the Year.
Papers were nominated and selected by the ISV Fellows and Board. The paper with the most votes in its category was selected paper of the year.
2022 ISV PAPER of the YEAR:
A vaccine targeting resistant tumours by dual T cell plus NK cell attack.
Badrinath S, Dellacherie MO, Li A, Zheng S, Zhang X, Sobral M, Pyrdol JW, Smith KL, Lu Y, Haag S, Ijaz H, Connor-Stroud F, Kaisho T, Dranoff G, Yuan GC, Mooney DJ, Wucherpfennig KW.
Nature. 2022 Jun;606(7916):992-998. doi: 10.1038/s41586-022-04772-4. Epub 2022 May 25. PMID: 35614223.
Abstract
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 presentation1. 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 damage2. 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 cleavage3,4. 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.