Human profilin 1 is a negative regulator of CTL mediated cell‐killing and migration
Open accessAbstract
The actin‐binding protein profilin1 (PFN1) plays a central role in actin dynamics, which is essential for cytotoxic T lymphocyte (CTL) functions. The functional role of PFN1 in CTLs, however still remains elusive. Here, we identify PFN1 as the only member of the profilin family expressed in primary human CD8+ T cells. Using in vitro assays, we find that PFN1 is a negative regulator of CTL‐mediated elimination of target cells. Furthermore, PFN1 is involved in activation‐induced lytic granule (LG) release, CTL migration and modulation of actin structures at the immunological synapse (IS). During CTL migration, PFN1 modulates the velocity, protrusion formation patterns and protrusion sustainability. In contrast, PFN1 does not significantly affect migration persistence and the rates of protrusion emergence and retraction. Under in vitro conditions mimicking a tumor microenvironment, we show that PFN1 downregulation promotes CTL invasion into a 3D matrix, without affecting the viability of CTLs in a hydrogen peroxide‐enriched microenvironment. Highlighting its potential relevance in cancer, we find that in pancreatic cancer patients, PFN1 expression is substantially decreased in peripheral CD8+ T cells. Taken together, we conclude that PFN1 is a negative regulator for CTL‐mediated cytotoxicity and may have an impact on CTL functionality in a tumor‐related context.
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PFN1 participates in actin organization and inhibits CD8+ cytotoxicity by reducing migration and degranulation.
“PFN1 is involved in actin organization, which inhibits CD8+ cytotoxicity by reducing migration and degranulation (45).”
From The Blood Proteoform Atlas: A reference map of proteoforms in human hematopoietic cells (2022) · cites this paper as [45]
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Self-citationTkachev, V., Kaminski, J., Potter, E. L., Furlan, S. N., Yu, A., Hunt, D. J., McGuckin, C., Zheng, H. B., Colonna, L., Gerdemann, U., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.20.212399
Profilin and Its Isoforms: Unravelling the Functional Diversity Across Life Forms
Pathak, N., & Kohila, V. (2025) · Current Protein and Peptide Science · doi:10.2174/0113892037390621250901052506
Shin, E., Yun, S. G., & Cho, Y. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.01.697324
Mpox virus immunology: exploring links to autoimmune diseases
Velasco-Lancheros, O. J., Acosta‐Ampudia, Y., Monsalve, D. M., & Ramı́rez-Santana, C. (2026) · Current Opinion in Immunology · doi:10.1016/j.coi.2026.102744
Alves-Pereira, C., Kim, G. D., Sherpa, N. D., Colvin, K., Khan, S. M., Phan, K. P., Wang, A. Z., Dunn, I. F., Johanns, T. M., Tsitsykov, E., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.11.724432
- Authors
- Schoppmeyer, R., Zhao, R., Cheng, H., Hamed, M., Liu, C., Zhou, X., Schwarz, E. C., Zhou, Y., Knörck, A., Schwär, G., Ji, S., Liu, L., Long, J., Helms, V., Hoth, M., Yu, X., & Qu, B.
- Affiliations
- Saarland University (DE)
- Department of Pancreatic and Hepatobiliary Surgery Fudan University Shanghai Cancer Center P.R. China
- Universitätsmedizin Rostock (DE)
- Shanghai Medical College of Fudan University (CN)
- Corresponding author
- Qu, Bin
- ORCID
- Venue
- European Journal of Immunology
- Publisher
- Wiley
- Published
- 2017-07-31
- Volume
- 47
- Issue
- 9
- Pages
- 1562-1572
- ISSN
- 0014-2980 (ISSN-L)
- 1521-4141
- OpenAlex
- W2730281647
- Cited by
- 50
- References
- 45
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 1 · 2023: 6 · 2022: 9 · 2021: 11 · 2020: 10 · 2019: 2 · 2018: 3
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81370065, 81172276, 81372653)
- Deutsche Forschungsgemeinschaft (GZ: INST 256/4 19‐1 FUGG)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- profilin-1, cytotoxic T lymphocytes, CD8+ T cells, actin dynamics, immunological synapse, actin protrusions, tumor microenvironment, pancreatic cancer, T cell cytotoxicity
- MeSH terms
- Cell Movement, Cells, Cultured, Cytotoxicity, Immunologic, Extracellular Matrix, Humans, Hydrogen Peroxide, Lymphocyte Activation, Actin Cytoskeleton, Pancreatic Neoplasms, T-Lymphocytes, Cytotoxic, Down-Regulation, Gene Expression Regulation, Neoplastic, CD8 Antigens, Cell Surface Extensions, Profilins, Immunological Synapses, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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