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We are analyzing https://www.nature.com/articles/s41467-021-21445-4.

Title:
Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation | Nature Communications
Description:
Immunotherapy has raised high expectations in the treatment of virtually every cancer. Many current efforts are focused on ensuring the efficient delivery of active cytotoxic cells to tumors. It is assumed that, once these active cytotoxic cells are correctly engaged to cancer cells, they will unfailingly eliminate the latter, provided that inhibitory factors are in check. T cell bispecific antibodies (TCBs) and chimeric antigen receptors (CARs) offer an opportunity to test this assumption. Using TCB and CARs directed against HER2, here we show that disruption of interferon-gamma signaling confers resistance to killing by active T lymphocytes. The kinase JAK2, which transduces the signal initiated by interferon-gamma, is a component repeatedly disrupted in several independently generated resistant models. Our results unveil a seemingly widespread strategy used by cancer cells to resist clearance by redirected lymphocytes. In addition, they open the possibility that long-term inhibition of interferon-gamma signaling may impair the elimination phase of immunoediting and, thus, promote tumor progression. Several mechanisms of resistance to T cell-engaging therapies have been described for solid tumors. Here, by using T cell bispecific antibodies and chimeric antigen receptors (CAR) T cells targeting HER2, the authors show that cancer cell intrinsic disruption of interferon-gamma signalling, including downregulation of JAK2, confers resistance to T-cell mediated cytotoxicity.
Website Age:
30 years and 10 months (reg. 1994-08-11).

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🌆 Monumental Traffic: 20M - 50M visitors per month


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Keywords {🔍}

cells, fig, ifnγ, cell, jak, resistance, resistant, hertcb, article, treated, tumor, btr, cancer, supplementary, min, google, scholar, data, levels, pbmcs, samples, signaling, lymphocytes, cas, car, parental, antibody, incubated, nature, treatment, killing, results, experiments, obtained, target, mice, cars, analysis, antibodies, tumors, ifngr, buffer, redirected, μgml, performed, expression, vivo, flow, analyzed, source,

Topics {✒️}

nature portfolio org/web/packages/pheatmap/index imaging ny-eso-1/lage-1-derived epitopes privacy policy cells promotes regional pmsgv1-her2-vl-vh-h8 advertising era-net transcan-2 initiative carlos alberto fajardo graft-versus-host disease nature 459 nature received research funds io/ reprints secondary antibody anti-biotin full development open enhancing n-glycan branching providing research facilities quantitative real-time pcr triple-negative breast cancer pan-hdac inhibitor trichostatin rnaseq libraries roche pharmaceutical research fixation/permeabilization working solution final library impaired ifn-γ signaling substrate ac-iepd-pna infinite m200 pro high lymphoma-directed cytotoxicity disrupting ifn-γ signaling unrestricted access early development catalytic p300/cbp inhibition anti-human ifn-γ tcr/mhc-antigen synapses thermo fisher scientific lenti-cas9-2a-blast antonio luque dimeric ifn-γ triggers assess t-cell activation irene rius ruiz macarena román alonso cells requires ifn-γ ifn-γ signaling pathway therapeutic cancer immunity tcr/mhc–antigen complex joaquín arribas horseradish peroxidase-conjugates antibodies

Questions {❓}

  • JAK2 inhibitors for myeloproliferative neoplasms: what is next?
  • Gov/bioproject/?

Schema {🗺️}

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      name:Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
      name:Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
      name:Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
      name:Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
      name:Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
      name:Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
      name:Tumor Immunology & Immunotherapy Group, VHIO, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
      name:Tumor Immunology & Immunotherapy Group, VHIO, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
      name:Roche Innovation Center Zurich, Roche Pharmaceutical Research and Early Development, Schlieren, Switzerland
      name:Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
      name:Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
      name:Department of Biochemistry and Molecular Biology, Universitat Autónoma de Barcelona (UAB), Bellaterra, Spain
      name:Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
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