Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts.

By Ela Elyada, M. Bolisetty, P. Laise, W. Flynn, Elise T. Courtois, R. Burkhart, J. Teinor, P. Belleau, Giulia Biffi, M. Lucito and 12 more. Cancer Discovery, 2019

1,681 citations recorded by the source corpus.

Cancer-associated fibroblasts (CAFs) are major players in the progression and drug resistance of pancreatic ductal adenocarcinoma (PDAC). CAFs constitute a diverse cell population consisting of several recently described subtypes, although the extent of CAF heterogeneity has remained undefined. Here we employ single-cell RNA sequencing to thoroughly characterize the neoplastic and tumor microenvironment content of human and mouse PDAC tumors. We corroborate the presence of myofibroblastic CAFs (myCAFs) and inflammatory CAFs (iCAFs) and define their unique gene signatures in vivo. Moreover, we describe a new population of CAFs that express MHC class II and CD74, but do not express classical co-stimulatory molecules. We term this cell population "antigen-presenting CAFs" (apCAFs), and find that they activate CD4+ T cells in an antigen-specific fashion in a model system, confirming their putative immune-modulatory capacity. Our cross-species analysis paves the way for investigating distinct functions of CAF subtypes in PDAC immunity and progression.

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/3ed96c101a788b25f1b5005a28bfd17fb0f9afc7

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Harald Schuhwerk
2. Thomas Brabletz
3. Simone Brabletz
4. Marc P. Stemmler

In Molecular Biology

1. Simone Brabletz
2. Thomas Brabletz
3. Marc P. Stemmler
4. Harald Schuhwerk
5. R. Weinberg
6. M. Nieto
7. D. Hanahan

In Oncology

1. Simone Brabletz
2. Thomas Brabletz
3. Harald Schuhwerk
4. Marc P. Stemmler
5. R. Weinberg
6. M. Nieto
7. D. Hanahan

Citations in the corpus

• Extracellular matrix remodeling in tumor progression and immune escape: from mechanisms to treatments (2023, background): “After that, MHC class IIexpressing antigen presenting CAFs (apCAFs) have been identified, and their role in stimulating activation of CD4 T cells via antigen-specific manner has been uncovered [338].”
• Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer. (2020, background): “org clusters (1, 2, 5) belong to the inflammatory (“iCAF”) subgroup and five CAF-S1 clusters (0, 3, 4, 6, 7) to the myofibroblastic (“myCAF”) subgroup, iCAF and myCAF having been previously identified in pancreatic cancer (7, 16, 26).”
• Dynamic EMT: a multi‐tool for tumor progression (2021, positive): “CAFs can be categorized into different subpopulations with specific functions and spatial organization (Lambrechts et al , 2018; Elyada et al , 2019; Sahai et al , 2020).”
• Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives (2021, background): “Subsequently, the presence of myCAFs and iCAFs in pancreatic cancer was confirmed through dropletbased single-cell transcriptomics technology [92].”