Activating a B cell immune response regresses immunologically cold tumours
Source abstract
Abstract
Progress in immuno-oncology has been stymied by poorly immunogenic 'cold' tumours and the focus on T cells at the cost of other immune cells. Here we report that AT-1965, a small molecule in a lipid nanoparticle, induces rapid regression of poorly immunogenic tumours with the formation of immune memory through interaction with Cap-specific RNA (nucleoside-2'-O-)-methyltransferase 2 (CMTR2) in cancer cells, triggering an innate inflammatory viral defence response. AT-1965-treated tumours were found to be highly infiltrated with B cells, which are known to act as early responders to viral signatures. Genetic knockout of functional B cells abrogated the anti-tumour efficacy of AT-1965, directly implicating B cells in the anti-tumour outcome. Our results rationalize clinical data showing that patients with high CMTR2 expression in tumours have a poor prognosis and that B cell infiltration is associated with long-term survival in multiple tumour types. The AT-1965 nanomedicine-inspired discovery of CMTR2 as a potential cancer target and B cell recruitment opens a new frontier for immuno-oncology.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: interferon and immune responses · Cancer Immunotherapy and Biomarkers · Immune cells in cancer
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (70)
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