This change may decrease the probability of contact between antigen-specific T lymphocytes and antigen-presenting cells carrying corresponding antigens, thereby further weakening the T cell immune response in vivo. This explains the effective homing ability of naive T cells to SLOs. The secretion of these chemokines in SLOs is not constant, but may be changed in different situations. Additionally, splenic expression of CCL21 and CCL19 is also reduced in inflammatory melanomas; however, the reasons for this have yet to be elucidated.
The results of the present study demonstrated that the splenic expression of CCL21 and CCL19 is reduced following chemotherapy and provided evidence that chemotherapy may downregulate the homing ability of T cells to the splenic SLOs, and that this is primarily caused by the downregulation of chemokines in splenic T cells. SLOs contain several compartments characterized by specific resident stromal cells, and the most important compartments are the B-cell and T-cell zones The B-cell zone is composed of follicular dendritic cells, which produce C-X-C chemokine ligand 13 to attract B cells.
In addition to killing tumor cells, chemotherapy, when reaching the blood, is also able to kill other normal tissue cells without any selectivity 6 , 7. The results of the present study demonstrated that chemotherapeutic drugs also induce injury to FRCs, causing cell death and weakening the ability of chemokine secretion. This also explains why the expression of chemokines in SLOs is reduced following chemotherapy and further suggests that, in addition to lymphocytopenia, chemotherapeutic drugs also affect the immune response of T cells through their impact on SLOs.
In addition to the spleen, another major component of SLOs is lymph nodes. However, the results of the present study suggested that chemotherapy does not affect the homing ability of T cells to the lymph nodes or the chemokine expression in the lymph nodes. We hypothesized that this may be due to the difference in anatomic structures between the lymph nodes and the spleen. The spleen is rich in blood vessels; it filters the old red blood cells and directly interacts with pathogens, small grains and foreign antigens in the blood As a result, it is hypothesized that the concentrations of chemotherapeutic drugs are higher in the spleen compared with concentrations in the lymph nodes.
Therefore, chemotherapeutic drugs exert different effects on the chemokine-secretory ability of the spleen and the lymph nodes. To conclude, cytotoxic chemotherapy may weaken the homing ability of T cells to the T-cell zone of the spleen. These observations aid in improving understanding of the mechanism underlying the decreased T cell immune response following repeated cycles of chemotherapy.
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. BG and BZ designed the study.
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LL and LZ performed experiments and prepared the manuscript. CH was involved in the acquisition of data for the flow cytometry. CH and LZ were involved in the preparation and revision of this manuscript. All authors approved the final version of this manuscript.
Bodey GP: Infection in cancer patients.
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Front Immunol. Nat Immunol. Cesta MF: Normal structure, function, and histology of the spleen. Toxicol Pathol. J Immunol. J Clin Oncol. Biochem Pharmacol. Cancer Res. Int J Mol Sci. Cell Immunol. Cancer Chemother Pharmacol. Bruserud O, Bergheim J, Shammas FV and Nesthus I: Serum concentrations of tumour necrosis factor-alpha during chemotherapy-induced leukopenia in patients with acute leukaemia and bacterial infections.
I agree. Home Submit Manuscript My Account. Advanced Search. Register Login. Oncology Letters. Cited By CrossRef : 0 citations. This article is mentioned in:. Finally, the present study identified that chemotherapy affects the function and survival of fibroblastic reticular cells in SLOs, which are the main source of CCL21 and CCL Introduction Chemotherapy is a major therapeutic tool for a diverse range of tumor types and serves an irreplaceable role in the majority of them.
Adoptive transfers and cell migration in vivo For T cell isolation, naive T cells were isolated using anti-CD3 magnetic beads cat.
Statistical analysis Multiple group comparisons were performed using a one-way analysis of variance, followed by Dunnett's multiple comparison test on GraphPad Prism software version 5. Results Chemotherapy weakens the homing ability of T cells to the T-cell zone of spleen The generation of the T cell immune response requires rare antigen-specific T cells to encounter DCs that present the appropriate antigen.
Related Articles. The protocol describes the DQ-Red BSA trafficking assay that can be used to study endocytic trafficking in various cell types.
Cells are constantly exchanging materials with their extracellular environment and in this process they internalize cargo in vesicles at the plasma membrane. This internalized cargo is delivered to the early endosomes from where it either goes back to the plasma membrane via recycling endosomes or enters the canonical endocytic pathway. Once destined to be degraded, the cargo moves to late endosomes and finally fuses with lysosomes where the active hydrolases digest the cargo Jovic et al.
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These endocytic compartments have characteristic pH of their lumen. The early endosomes have a pH in the range of 5. The acidic environment of lysosomes is necessary for the activity of hydrolases present in its lumen and degradation of cargo Garg et al.