Back to Search
Start Over
Keratin 17 modulates the immune topography of pancreatic cancer.
- Source :
-
Journal of translational medicine [J Transl Med] 2024 May 10; Vol. 22 (1), pp. 443. Date of Electronic Publication: 2024 May 10. - Publication Year :
- 2024
-
Abstract
- Background: The immune microenvironment impacts tumor growth, invasion, metastasis, and patient survival and may provide opportunities for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC). Although never studied as a potential modulator of the immune response in most cancers, Keratin 17 (K17), a biomarker of the most aggressive (basal) molecular subtype of PDAC, is intimately involved in the histogenesis of the immune response in psoriasis, basal cell carcinoma, and cervical squamous cell carcinoma. Thus, we hypothesized that K17 expression could also impact the immune cell response in PDAC, and that uncovering this relationship could provide insight to guide the development of immunotherapeutic opportunities to extend patient survival.<br />Methods: Multiplex immunohistochemistry (mIHC) and automated image analysis based on novel computational imaging technology were used to decipher the abundance and spatial distribution of T cells, macrophages, and tumor cells, relative to K17 expression in 235 PDACs.<br />Results: K17 expression had profound effects on the exclusion of intratumoral CD8+ T cells and was also associated with decreased numbers of peritumoral CD8+ T cells, CD16+ macrophages, and CD163+ macrophages (p < 0.0001). The differences in the intratumor and peritumoral CD8+ T cell abundance were not impacted by neoadjuvant therapy, tumor stage, grade, lymph node status, histologic subtype, nor KRAS, p53, SMAD4, or CDKN2A mutations.<br />Conclusions: Thus, K17 expression correlates with major differences in the immune microenvironment that are independent of any tested clinicopathologic or tumor intrinsic variables, suggesting that targeting K17-mediated immune effects on the immune system could restore the innate immunologic response to PDAC and might provide novel opportunities to restore immunotherapeutic approaches for this most deadly form of cancer.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Tumor Microenvironment immunology
Female
Carcinoma, Pancreatic Ductal immunology
Carcinoma, Pancreatic Ductal pathology
Male
CD8-Positive T-Lymphocytes immunology
Macrophages metabolism
Macrophages immunology
Middle Aged
Aged
Receptors, Cell Surface
Antigens, Differentiation, Myelomonocytic
Antigens, CD
Keratin-17 metabolism
Pancreatic Neoplasms immunology
Pancreatic Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1479-5876
- Volume :
- 22
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 38730319
- Full Text :
- https://doi.org/10.1186/s12967-024-05252-1