Evidence map›Paper›PMID 38464123›Full record

ArticleResearch square2024

Keratin 17 modulates the immune topography of pancreatic cancer.

Lyanne A Delgado-Coka, Michael Horowitz, Mariana Torrente-Goncalves, Lucia Roa-Peña, Cindy V Leiton, Mahmudul Hasan, Sruthi Babu, Danielle Fassler, Jaymie Oentoro, Ji-Dong Karen Bai and 15 more

Open access · greenAbstract readPreprint
In one paragraph

Article in Research square, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 7 institutions in 3 countries.

Lyanne A Delgado-CokaStony Brook University.
Michael HorowitzStony Brook University.
Mariana Torrente-GoncalvesStony Brook University.
Lucia Roa-PeñaUniversidad Nacional de Colombia.
Cindy V LeitonStony Brook University.
Mahmudul HasanStony Brook University.
Sruthi BabuStony Brook University.
Danielle FasslerStony Brook University.
Jaymie OentoroStony Brook University.
Ji-Dong Karen BaiStony Brook University.
Emanuel F PetricoinPerthera Inc.
Lynn M MatrisianStony Brook University.
Edik Matthew BlaisPerthera Inc.
Natalia MarchenkoStony Brook University.
Felicia D AllardUniversity of Arkansas.
Wei JiangThomas Jefferson University.
Brent LarsonCedars-Sinai: Cedars-Sinai Health System.
Andrew HendifarCedars-Sinai: Cedars-Sinai Health System.
Chao ChenStony Brook University.
Shahira AbousamraStony Brook University.
Dimitris SamarasStony Brook University.
Tahsin KurcStony Brook University.
Joel SaltzStony Brook University.
Luisa F Escobar-HoyosYale University.
Kenneth ShroyerStony Brook University.
Stony Brook University · USYale University · USXperi (Ireland) · IESinai Health System · USThomas Jefferson University · USUniversidad Nacional de Colombia · COUniversity of Arkansas at Fayetteville · US

Funding

TCIA Sustainment and Scalability - Platforms for Quantitative Imaging Informatics in Precision MedicineU24CA215109 · NCI · UNIV OF ARKANSAS FOR MED SCIS · PI BANERJEE, IMON, PRIOR, FRED WILLIAM · 2017 to 2021
$8.5M
Unleashing T-cell anti-tumor response through repair of altered RNA splicing and antigen mimicry recognitionDP2CA280625 · NCI · YALE UNIVERSITY · PI ESCOBAR HOYOS, LUISA · 2022 to 2025
$2.5M
Understanding and targeting mutant splicing factors in pancreatic cancerR01CA274355 · NCI · YALE UNIVERSITY · PI ESCOBAR HOYOS, LUISA · 2022 to 2025
$2.4M
Methods and Tools for Integrating Pathomics Data into Cancer RegistriesUH3CA225021 · NCI · STATE UNIVERSITY NEW YORK STONY BROOK · PI CLIFFORD, GARI DAVID, DURBIN, ERIC B. · 2020 to 2022
$1.9M
Altered mRNA splicing dependent on mutant p53 identifies novel therapeutic vulnerability in pancreatic cancerR00CA226342 · NCI · YALE UNIVERSITY · PI ESCOBAR HOYOS, LUISA · 2020 to 2022
$741k
Altered mRNA splicing dependent on mutant p53 identifies novel therapeutic vulnerability in pancreatic cancerK99CA226342 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ESCOBAR HOYOS, LUISA · 2018 to 2019
$204k
NCI NIH HHS DP2 CA280625NCI NIH HHS K99 CA226342NCI NIH HHS R00 CA226342NCI NIH HHS R01 CA274355NCI NIH HHS U24 CA215109NCI NIH HHS UH3 CA225021
6 · The paper itself

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. 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. 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. 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.

Indexed as

cancer biomarkercancer immunologydigital pathologyimmune microenvironmentkeratin 17multiplexed immunohistochemistrypancreatic ductal adenocarcinoma

Identifiers

PMID38464123
PMCPMC10925455
OpenAlexW4391987451

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.