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Immunoprofiles of c...
Immunoprofiles of colorectal cancer from Lynch syndrome
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- Walkowska, Joanna (author)
- Hvidovre Hospital
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- Kallemose, Thomas (author)
- Hvidovre Hospital
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- Jönsson, Göran (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Jönsson, Mats (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Forskningsgrupp Lungcancer,Forskargrupper vid Lunds universitet,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Research Group Lung Cancer,Lund University Research Groups
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- Andersen, Ove (author)
- Hvidovre Hospital
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- Andersen, Mads Hald (author)
- Herlev Hospital
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- Svane, Inge Marie (author)
- Herlev Hospital
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- Langkilde, Anne (author)
- Hvidovre Hospital
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- Nilbert, Mef (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Hvidovre Hospital,Danish Cancer Society
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- Therkildsen, Christina (author)
- Hvidovre Hospital
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(creator_code:org_t)
- 2019
- 2019
- English.
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In: OncoImmunology. - 2162-4011. ; 8:1
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- familial colorectal cancer type X
- Hereditary non-polyposis colorectal cancer
- immunophenotypes
- microsatellite instability
- mismatch repair
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Walkowska, Joann ...
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Kallemose, Thoma ...
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Jönsson, Göran
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Jönsson, Mats
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Andersen, Ove
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Andersen, Mads H ...
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show more...
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Svane, Inge Mari ...
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Langkilde, Anne
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Nilbert, Mef
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Therkildsen, Chr ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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OncoImmunology
- By the university
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Lund University