Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer
Open accessAbstract
Abstract The exact nature and dynamics of pancreatic ductal adenocarcinoma (PDAC) immune composition remains largely unknown. Desmoplasia is suggested to polarize PDAC immunity. Therefore, a comprehensive evaluation of the composition and distribution of desmoplastic elements and T-cell infiltration is necessary to delineate their roles. Here we develop a novel computational imaging technology for the simultaneous evaluation of eight distinct markers, allowing for spatial analysis of distinct populations within the same section. We report a heterogeneous population of infiltrating T lymphocytes. Spatial distribution of cytotoxic T cells in proximity to cancer cells correlates with increased overall patient survival. Collagen-I and αSMA + fibroblasts do not correlate with paucity in T-cell accumulation, suggesting that PDAC desmoplasia may not be a simple physical barrier. Further exploration of this technology may improve our understanding of how specific stromal composition could impact T-cell activity, with potential impact on the optimization of immune-modulatory therapies.
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Previous studies demonstrated that the amount of active T-cells is positively correlated with the success of immune checkpoint blockade therapy.
“Previous studies have demonstrated that the amount of active T-cells is positively correlated with the success of immune checkpoint blockade therapy36,37”
From Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer (2020) · cites this paper as [37]
The Abstract links endogenous antitumour T cells to the efficacy of therapies combined with checkpoint blockade. But it does not report a positive correlation between the amount of active T cells and checkpoint-blockade success. The Discussion states that T-cell functional status was not measured; page numbers are unavailable in our copy. (LLM, conf=0.86)
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- Authors
- Carstens, J. L., Correa de Sampaio, P., Yang, D., Barua, S., Wang, H., Rao, A., Allison, J. P., LeBleu, V. S., & Kalluri, R.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Kalluri, Raghu
- ORCID
- Venue
- Nature Communications
- Published
- 2017-04-27
- Volume
- 8
- Issue
- 1
- Pages
- 15095-15095
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5414182
- OpenAlex
- W2609921003
- Cited by
- 633
- References
- 3
- Citations by year
- 2026: 40 · 2025: 68 · 2024: 82 · 2023: 102 · 2022: 74 · 2021: 89 · 2020: 65 · 2019: 53 · 2018: 43 · 2017: 10 · 2015: 1
- FWCI
- 20.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Cancer Prevention and Research Institute of Texas (RP-110532, P30CA016672, CA016672)
- Lustgarten Foundation
- Nvidia
- National Institutes of Health (CA- 016672, RSG-16-005-01, / NCI P 30 CA016672)
- University of Texas MD Anderson Cancer Center (NCI P30CA016672, (CA016672), P30-CA-016672, grant CA016672)
- National Cancer Institute (Grant CA016672, CA 016672, NCI P30CA016672, CA196403, CA117969, U01CA196403, P30CA016672, P01CA117969, P50CA127001)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- pancreatic ductal adenocarcinoma, intratumoral T cells, desmoplasia, T cell infiltration, spatial imaging, cytotoxic T lymphocytes, patient survival, type I collagen, alpha-smooth muscle actin, cancer-associated fibroblasts, tumor microenvironment, immunomodulatory therapy
- MeSH terms
- Actins, Adult, Aged, Aged, 80 and over, Animals, Female, Fibroblasts, Humans, Immunohistochemistry, Male, Middle Aged, Pancreatic Neoplasms, Prognosis, Spectrum Analysis, T-Lymphocytes, T-Lymphocytes, Cytotoxic, Survival Rate, Lymphocytes, Tumor-Infiltrating, Carcinoma, Pancreatic Ductal, Collagen Type I, Tissue Array Analysis, Mice, Spatial Analysis
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