Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Immunoprofiles of colorectal cancer from Lynch syndrome

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Neo-antigen specific memory T-cell responses in healthy individuals

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4+ T cells in cutaneous T-cell lymphoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. T cell recognition of novel shared breast cancer antigens is frequently observed in peripheral blood of breast cancer patients

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Adoptive cell therapy with tumor-infiltrating lymphocytes in patients with metastatic ovarian cancer: a pilot study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  2. Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Meet the Acta Oncologica editorial board

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Colorectal cancers associated with Lynch syndrome are characterized by defective mismatch repair, microsatellite instability, high mutation rates, and a highly immunogenic environment. These features define a subset of cancer with a favorable prognosis and high likelihood to respond to treatment with anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) drugs. With the aim to define immune-evasive mechanisms and a potential impact hereof in colorectal cancers from Lynch syndrome versus hereditary cases with retained mismatch repair function, we immunohistochemically and transcriptionally profiled 270 tumors. Lynch syndrome-associated tumors showed an overrepresentation of tumor-infiltrating CD3, CD8 and CD68 positive cells, loss of beta-2-microglobulin (B2M) and up-regulation of PD-L1 on tumor cells. The gene expression signature of Lynch syndrome tumors was characterized by upregulation of genes related to antigen processing and presentation, apoptosis, natural killer cell-mediated cytotoxicity, and T cell activation. Tumors with loss of B2M and up-regulation of PD-L1 showed distinctive immunogenic profiles. In summary, our data demonstrate a complex tumor-host interplay where B2M loss and PD-L1 up-regulation influence immunological pathways and clinical outcome in Lynch syndrome tumors. Immunological classification may thus aid in the preselection of colorectal cancers relevant for treatment with anti-PD-1/PD-L1 therapies.

OriginalsprogEngelsk
Artikelnummere1515612
TidsskriftOncoImmunology
Vol/bind8
Udgave nummer1
Sider (fra-til)e1515612
ISSN2162-4011
DOI
StatusUdgivet - 2019

ID: 55855874