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Peer-reviewedCC BY 4.0Frontiers in Immunology

Chemokines as regulators of CAR-T cell trafficking, function, and context-dependent tumor cell death

  • Ksenia Levchuk1,2
  • Alexey Petukhov2,3,4
  • Shynggys Tursymbek2,3
  • Kuanysh Seitkamal3
  • Arailym Bertleuova3
  • Denis Bulanin3
  • Nikolai A. Barlev2,3
4 affiliations
  1. 1Institute of Cytology, Russian Academy of Sciences
  2. 2Laboratory of Molecular Oncology, National Laboratory Astana
  3. 3Department of Biomedical Sciences, School of Medicine, Nazarbayev University
  4. 4Limited Liability Partnership (LLP) Center of Hematology
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Abstract

Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of hematological malignancies, yet its efficacy in solid tumors remains limited by inefficient trafficking, suppressive myeloid and regulatory T-cell populations, and metabolic stress. These barriers contribute to incomplete tumor cell killing and loss of CAR-T cell function. Chemokines are usually viewed as migratory guides, but in solid tumors they also orchestrate immune cell positioning and inflammatory state. In this review, we discuss how chemokine gradients form inflammatory niches and control CAR-T-cell recruitment, intratumoral distribution, retention, and egress. We also examine how chemokine programs interact with cytokine signaling and regulated tumor cell death to shape local and potentially tissue-wide antitumor immunity, including through the release of damage-associated molecular patterns (DAMPs). Finally, we outline translational strategies that include engineered chemokines and matched chemokine receptor programs to enhance the efficacy of chemokine/cytokine-armored CAR-T cells, and related combination therapies.

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Cite

BibTeXRIS
BibTeX
@article{levchuk2026chemokines,
  title = {{Chemokines as regulators of CAR-T cell trafficking, function, and context-dependent tumor cell death}},
  author = {Ksenia Levchuk and Alexey Petukhov and Shynggys Tursymbek and Kuanysh Seitkamal and Arailym Bertleuova and Denis Bulanin and Nikolai A. Barlev},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1963794},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1963794/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Chemokines as regulators of CAR-T cell trafficking, function, and context-dependent tumor cell death
AU  - Ksenia Levchuk
AU  - Alexey Petukhov
AU  - Shynggys Tursymbek
AU  - Kuanysh Seitkamal
AU  - Arailym Bertleuova
AU  - Denis Bulanin
AU  - Nikolai A. Barlev
PY  - 2026
DA  - 2026/10/07
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1963794
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1963794/full
AB  - Chimeric antigen receptor (CAR)-T cell therapy has transformed the treatment of hematological malignancies, yet its efficacy in solid tumors remains limited by inefficient trafficking, suppressive myeloid and regulatory T-cell populations, and metabolic stress. These barriers contribute to incomplete tumor cell killing and loss of CAR-T cell function. Chemokines are usually viewed as migratory guides, but in solid tumors they also orchestrate immune cell positioning and inflammatory state. In this review, we discuss how chemokine gradients form inflammatory niches and control CAR-T-cell recruitment, intratumoral distribution, retention, and egress. We also examine how chemokine programs interact with cytokine signaling and regulated tumor cell death to shape local and potentially tissue-wide antitumor immunity, including through the release of damage-associated molecular patterns (DAMPs). Finally, we outline translational strategies that include engineered chemokines and matched chemokine receptor programs to enhance the efficacy of chemokine/cytokine-armored CAR-T cells, and related combination therapies.
SN  - 1664-3224
ER  -