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Cryo-ablation improves anti-tumor immunity through recovering tumor educated dendritic cells in tumor-draining lymph nodes.

He XZ, Wang QF, Han S, Wang HQ, Ye YY, Zhu ZY, Zhang SZ - Drug Des Devel Ther (2015)

Bottom Line: Moreover, the DCs decreased the expression of intracellular interleukin-10 (IL-10) and extra-cellular IL-10.More importantly, Tregs inhibited the performance of these DCs; and depletion of Tregs greatly improved anti-tumor immunity in vivo.The Tregs/CD4(+)T and Tregs/CD25(+)T cells in TDLNs inhibit DCs' activity and function.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China ; The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, People's Republic of China.

ABSTRACT

Background: In addition to minimally invasive destruction of tumors, cryo-ablation of tumors to some extent modulated anti-tumor immunity. Cryo-ablated tumors in glioma mice models induced anti-tumor cellular immunologic response which increases the percentage of CD3(+) and CD4(+)T cells in blood as well as natural killer cells. As a crucial role in triggering anti-tumor immunity, dendritic cells (DCs) were educated by tumors to adopt a tolerance phenotype which helps the tumor escape from immune monitoring. This study aims to study whether cryo-ablation could influence the tolerogenic DCs, and influence anti-tumor immunity in tumor-draining lymph nodes (TDLNs).

Methods: Using the GL261 subcutaneous glioma mouse model, we created a tumor bearing group, cryo-ablation group, and surgery group. We analyzed alteration in phenotype and function of tolerogenic DCs, and evaluated the factors of anti-tumor immunity inhibition.

Results: DCs in TDLNs in GL261 subcutaneous glioma mouse model expressed tolerogenic phenotype. In contrast to surgery, cryo-ablation improved the quantity and quality of these tolerogenic DCs. Moreover, the DCs decreased the expression of intracellular interleukin-10 (IL-10) and extra-cellular IL-10. In vitro, DCs from the cryo-ablation group recovered their specific function and induced potent anti-tumor immunity through triggering T cells. In vivo, cryo-ablation showed weak anti-tumor immunity, only inhibiting the growth of rechallenged tumors. But many IL-10-low DCs, rather than IL-10-high DCs, infiltrated the tumors. More importantly, Tregs inhibited the performance of these DCs; and depletion of Tregs greatly improved anti-tumor immunity in vivo.

Conclusion: Cryo-ablation could recover function of tumor induced tolerogenic DCs in vitro; and depletion of Tregs could improve this anti-tumor effect in vivo. The Tregs/CD4(+)T and Tregs/CD25(+)T cells in TDLNs inhibit DCs' activity and function.

No MeSH data available.


Related in: MedlinePlus

Cryo-ablation could delay tumor growth in tumor rechallenge and reduce the expression of IL-10 in tumor-infiltrating DCs.Notes: (A) Mice were re-injected 104 GL261 cells in the left flank. Tumors were measured every 4 to 5 days using Vernier calipers. Data are pooled from five mice/group. The tumor size in each group was also analyzed and compared between groups. (B) Second tumor-free survival was plotted as a Kaplan–Meier curve and the log rank test was used for statistical analysis. However, no significant difference was discovered in the tumor-free survival time of these three groups. (C) Immunofluorescence microscopy of 20 μm thick sections of second tumors from surgery group (top) and cryo-ablation group (bottom) were stained for CD11c (red) and IL-10 (green). DAPI was blue. Scale bar: 20 μm. The data are representative of three independent experiments. Statistical significance was calculated by one-way ANOVA using the Bonferroni post-test with the following notations for P-value. *P<0.05, error bars, SEM.Abbreviations: IL, interleukin; DCs, dendritic cells; DAPI, 4′,6-diamidino-2-phenylindole; ANOVA, analysis of variance; SEM, standard error of the mean.
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f4-dddt-9-1449: Cryo-ablation could delay tumor growth in tumor rechallenge and reduce the expression of IL-10 in tumor-infiltrating DCs.Notes: (A) Mice were re-injected 104 GL261 cells in the left flank. Tumors were measured every 4 to 5 days using Vernier calipers. Data are pooled from five mice/group. The tumor size in each group was also analyzed and compared between groups. (B) Second tumor-free survival was plotted as a Kaplan–Meier curve and the log rank test was used for statistical analysis. However, no significant difference was discovered in the tumor-free survival time of these three groups. (C) Immunofluorescence microscopy of 20 μm thick sections of second tumors from surgery group (top) and cryo-ablation group (bottom) were stained for CD11c (red) and IL-10 (green). DAPI was blue. Scale bar: 20 μm. The data are representative of three independent experiments. Statistical significance was calculated by one-way ANOVA using the Bonferroni post-test with the following notations for P-value. *P<0.05, error bars, SEM.Abbreviations: IL, interleukin; DCs, dendritic cells; DAPI, 4′,6-diamidino-2-phenylindole; ANOVA, analysis of variance; SEM, standard error of the mean.

Mentions: To examine the anti-tumor immune memory, we re-injected GL261 glioma cells into the left flank of mice. As shown in Figure 4A, tumor growth in the surgery group was the same as the control group (P>0.05), but in the cryo-ablation group, tumor grew (tumor size) significantly slower compared to the other groups (P<0.05). However, the Kaplan–Meier curve showed no significant difference in the tumor-free survival time of these three groups (Figure 4B). Immunofluorescence staining showed that rechallenged tumors were infiltrated with DCs, which expressed low IL-10 in cryo-ablated mice, but high IL-10 in surgery mice (Figure 4C).


Cryo-ablation improves anti-tumor immunity through recovering tumor educated dendritic cells in tumor-draining lymph nodes.

He XZ, Wang QF, Han S, Wang HQ, Ye YY, Zhu ZY, Zhang SZ - Drug Des Devel Ther (2015)

Cryo-ablation could delay tumor growth in tumor rechallenge and reduce the expression of IL-10 in tumor-infiltrating DCs.Notes: (A) Mice were re-injected 104 GL261 cells in the left flank. Tumors were measured every 4 to 5 days using Vernier calipers. Data are pooled from five mice/group. The tumor size in each group was also analyzed and compared between groups. (B) Second tumor-free survival was plotted as a Kaplan–Meier curve and the log rank test was used for statistical analysis. However, no significant difference was discovered in the tumor-free survival time of these three groups. (C) Immunofluorescence microscopy of 20 μm thick sections of second tumors from surgery group (top) and cryo-ablation group (bottom) were stained for CD11c (red) and IL-10 (green). DAPI was blue. Scale bar: 20 μm. The data are representative of three independent experiments. Statistical significance was calculated by one-way ANOVA using the Bonferroni post-test with the following notations for P-value. *P<0.05, error bars, SEM.Abbreviations: IL, interleukin; DCs, dendritic cells; DAPI, 4′,6-diamidino-2-phenylindole; ANOVA, analysis of variance; SEM, standard error of the mean.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362656&req=5

f4-dddt-9-1449: Cryo-ablation could delay tumor growth in tumor rechallenge and reduce the expression of IL-10 in tumor-infiltrating DCs.Notes: (A) Mice were re-injected 104 GL261 cells in the left flank. Tumors were measured every 4 to 5 days using Vernier calipers. Data are pooled from five mice/group. The tumor size in each group was also analyzed and compared between groups. (B) Second tumor-free survival was plotted as a Kaplan–Meier curve and the log rank test was used for statistical analysis. However, no significant difference was discovered in the tumor-free survival time of these three groups. (C) Immunofluorescence microscopy of 20 μm thick sections of second tumors from surgery group (top) and cryo-ablation group (bottom) were stained for CD11c (red) and IL-10 (green). DAPI was blue. Scale bar: 20 μm. The data are representative of three independent experiments. Statistical significance was calculated by one-way ANOVA using the Bonferroni post-test with the following notations for P-value. *P<0.05, error bars, SEM.Abbreviations: IL, interleukin; DCs, dendritic cells; DAPI, 4′,6-diamidino-2-phenylindole; ANOVA, analysis of variance; SEM, standard error of the mean.
Mentions: To examine the anti-tumor immune memory, we re-injected GL261 glioma cells into the left flank of mice. As shown in Figure 4A, tumor growth in the surgery group was the same as the control group (P>0.05), but in the cryo-ablation group, tumor grew (tumor size) significantly slower compared to the other groups (P<0.05). However, the Kaplan–Meier curve showed no significant difference in the tumor-free survival time of these three groups (Figure 4B). Immunofluorescence staining showed that rechallenged tumors were infiltrated with DCs, which expressed low IL-10 in cryo-ablated mice, but high IL-10 in surgery mice (Figure 4C).

Bottom Line: Moreover, the DCs decreased the expression of intracellular interleukin-10 (IL-10) and extra-cellular IL-10.More importantly, Tregs inhibited the performance of these DCs; and depletion of Tregs greatly improved anti-tumor immunity in vivo.The Tregs/CD4(+)T and Tregs/CD25(+)T cells in TDLNs inhibit DCs' activity and function.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China ; The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Southern Medical University, Guangzhou, People's Republic of China.

ABSTRACT

Background: In addition to minimally invasive destruction of tumors, cryo-ablation of tumors to some extent modulated anti-tumor immunity. Cryo-ablated tumors in glioma mice models induced anti-tumor cellular immunologic response which increases the percentage of CD3(+) and CD4(+)T cells in blood as well as natural killer cells. As a crucial role in triggering anti-tumor immunity, dendritic cells (DCs) were educated by tumors to adopt a tolerance phenotype which helps the tumor escape from immune monitoring. This study aims to study whether cryo-ablation could influence the tolerogenic DCs, and influence anti-tumor immunity in tumor-draining lymph nodes (TDLNs).

Methods: Using the GL261 subcutaneous glioma mouse model, we created a tumor bearing group, cryo-ablation group, and surgery group. We analyzed alteration in phenotype and function of tolerogenic DCs, and evaluated the factors of anti-tumor immunity inhibition.

Results: DCs in TDLNs in GL261 subcutaneous glioma mouse model expressed tolerogenic phenotype. In contrast to surgery, cryo-ablation improved the quantity and quality of these tolerogenic DCs. Moreover, the DCs decreased the expression of intracellular interleukin-10 (IL-10) and extra-cellular IL-10. In vitro, DCs from the cryo-ablation group recovered their specific function and induced potent anti-tumor immunity through triggering T cells. In vivo, cryo-ablation showed weak anti-tumor immunity, only inhibiting the growth of rechallenged tumors. But many IL-10-low DCs, rather than IL-10-high DCs, infiltrated the tumors. More importantly, Tregs inhibited the performance of these DCs; and depletion of Tregs greatly improved anti-tumor immunity in vivo.

Conclusion: Cryo-ablation could recover function of tumor induced tolerogenic DCs in vitro; and depletion of Tregs could improve this anti-tumor effect in vivo. The Tregs/CD4(+)T and Tregs/CD25(+)T cells in TDLNs inhibit DCs' activity and function.

No MeSH data available.


Related in: MedlinePlus