Preexisting malignancy abrogates the beneficial effects of CXCR4 blockade during sepsis
| Autor: | Zhe Liang, Deena B. Chihade, Craig M. Coopersmith, Kimberly M. Ramonell, Wenxiao Zhang, Ching-Wen Chen, Mandy L. Ford, Jianfeng Xie |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Antigens Differentiation T-Lymphocyte CD4-Positive T-Lymphocytes Male Benzylamines Receptors CXCR4 T cell Immunology Spleen Punctures Biology CD8-Positive T-Lymphocytes medicine.disease_cause Cyclams CXCR4 Article Sepsis 03 medical and health sciences 0302 clinical medicine Antigens CD Bone Marrow Heterocyclic Compounds Neoplasms medicine Immunology and Allergy Animals Lectins C-Type Cecum Ligation Cancer Cell Biology Immune dysregulation medicine.disease Blockade Up-Regulation Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Female Bone marrow Biomarkers |
| Zdroj: | J Leukoc Biol |
| ISSN: | 1938-3673 |
| Popis: | Patients with cancer are at an increased risk of developing and dying from sepsis. We previously reported that blockade of the chemokine receptor CXCR4 resulted in decreased CD4+ T cell exhaustion and improved survival in a model of polymicrobial sepsis in previously healthy mice. Here, we sought to determine whether CXCR4 blockade could improve mortality and immune dysregulation during sepsis complicated with malignancy. Results in animals inoculated with a lung cancer cell line and subjected to CLP 3 weeks later indicated that CXCR4 was up-regulated on naïve and central memory T cells following sepsis. Of note, and in contrast to results in previously healthy mice, CXCR4 blockade failed to improve survival in cancer septic animals; instead, it actually significantly worsened survival. In the setting of cancer, CXCR4 blockade failed to result in T cell egress from the bone marrow, reverse lymphopenia in the spleen, or reverse T cell exhaustion. Mechanistically, elevated expression of CD69 on naïve T cells in the bone marrow of cancer septic animals was associated with their inability to egress from the bone marrow in the setting of CXCR4 blockade. In conclusion, these results illuminate the differential impact of CXCR4 blockade on sepsis pathophysiology in the setting of cancer and highlight the need for personalized therapy during sepsis. |
| Databáze: | OpenAIRE |
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