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Tumor-specific immunity induced by cryoablation in a murine renal cell carcinoma model.

Kim HK, Pyun JH, Cho S, Kang SG, Lee JG, Kim JJ, Cheon J, Park HS, Kang SH - Korean J Urol (2014)

Bottom Line: The mice successfully treated were rechallenged with RENCA or an undifferentiated colon carcinoma cell line, CT26, in the contralateral right flank area.The cryoablation group showed an elevated CD3, CD4, CD8 T, and natural killer cell count in the FACS analysis and also showed significantly increased cytotoxicity in the (51)Cr release assay compared with the excision group.These results showed that cryoablation, compared to surgical resection, was more effective in preventing tumor growth after rechallenge with RENCA cells and that this response was tumor-specific, because the CT26 cells did not have the same effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Korea University Anam Hospital, Seoul, Korea.

ABSTRACT

Purpose: To evaluate tumor-specific immunity and define the mechanisms involved in the cryoimmunologic response, we compared the tumor control efficacy and immunologic responses of cryoablation with those of surgical excision in a tumor rechallenge model.

Materials and methods: Sixty BALB/c mice with RENCA tumors that were generated in the left flank area underwent cryoablation or radical excision. The mice successfully treated were rechallenged with RENCA or an undifferentiated colon carcinoma cell line, CT26, in the contralateral right flank area. The recurrence rate after tumor rechallenge in each group was then observed. To assess the immunologic response of each treatment modality, fluorescent-activated cell sorting (FACS) analysis and a cytotoxicity assay using (51)Cr release were performed.

Results: After reinoculation of the RENCA cells, the rate of tumor growth was significantly higher in the surgical excision group than in the cryoablation group (94.4% vs. 11.1%, p=0.001). In the cryoablation group, the tumor growth rate was significantly increased after rechallenge of CT26 cells compared with RENCA (94.1% vs. 11.1%, p=0.001). The cryoablation group showed an elevated CD3, CD4, CD8 T, and natural killer cell count in the FACS analysis and also showed significantly increased cytotoxicity in the (51)Cr release assay compared with the excision group.

Conclusions: These results showed that cryoablation, compared to surgical resection, was more effective in preventing tumor growth after rechallenge with RENCA cells and that this response was tumor-specific, because the CT26 cells did not have the same effect.

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Related in: MedlinePlus

Flowchart of tumor rechallenges. After 14 days of each treatment including surgical excision and cryoablation on the left side of the tumors induced by RENCA injection, the RENCA cells were reinjected on the right side of the BALB/c mice, which was free of tumor recurrence. To verify tumor specific immunity, for 20 mice treated with cryoablation and free of tumor recurrence, CT26 cells were injected in a similar manner. FACS, fluorescent-activated cell sorting.
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Figure 1: Flowchart of tumor rechallenges. After 14 days of each treatment including surgical excision and cryoablation on the left side of the tumors induced by RENCA injection, the RENCA cells were reinjected on the right side of the BALB/c mice, which was free of tumor recurrence. To verify tumor specific immunity, for 20 mice treated with cryoablation and free of tumor recurrence, CT26 cells were injected in a similar manner. FACS, fluorescent-activated cell sorting.

Mentions: At 14 days after the cryoablation or surgical excision, a secondary tumor rechallenge was performed in the right flank area in mice that were free of tumor recurrence at the previously treated left flank area (Fig. 1). For the surgical excision group, the same dose of RENCA cells (1×106) was injected subcutaneously to the right flank area. The mice treated by cryoablation were divided into two groups: half of them received 1×106 RENCA cells as a rechallenge, subcutaneously in the right flank area, and the other half received the same amount of CT26 cells for rechallenge in the right flank area. The growth patterns of the tumors were carefully evaluated for 28 days. Fluorescent-activated cell sorting (FACS) analysis and cytotoxicity assay were performed and compared between the RENCA rechallenge group after either excision or cryoablation (Fig. 1).


Tumor-specific immunity induced by cryoablation in a murine renal cell carcinoma model.

Kim HK, Pyun JH, Cho S, Kang SG, Lee JG, Kim JJ, Cheon J, Park HS, Kang SH - Korean J Urol (2014)

Flowchart of tumor rechallenges. After 14 days of each treatment including surgical excision and cryoablation on the left side of the tumors induced by RENCA injection, the RENCA cells were reinjected on the right side of the BALB/c mice, which was free of tumor recurrence. To verify tumor specific immunity, for 20 mice treated with cryoablation and free of tumor recurrence, CT26 cells were injected in a similar manner. FACS, fluorescent-activated cell sorting.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4265719&req=5

Figure 1: Flowchart of tumor rechallenges. After 14 days of each treatment including surgical excision and cryoablation on the left side of the tumors induced by RENCA injection, the RENCA cells were reinjected on the right side of the BALB/c mice, which was free of tumor recurrence. To verify tumor specific immunity, for 20 mice treated with cryoablation and free of tumor recurrence, CT26 cells were injected in a similar manner. FACS, fluorescent-activated cell sorting.
Mentions: At 14 days after the cryoablation or surgical excision, a secondary tumor rechallenge was performed in the right flank area in mice that were free of tumor recurrence at the previously treated left flank area (Fig. 1). For the surgical excision group, the same dose of RENCA cells (1×106) was injected subcutaneously to the right flank area. The mice treated by cryoablation were divided into two groups: half of them received 1×106 RENCA cells as a rechallenge, subcutaneously in the right flank area, and the other half received the same amount of CT26 cells for rechallenge in the right flank area. The growth patterns of the tumors were carefully evaluated for 28 days. Fluorescent-activated cell sorting (FACS) analysis and cytotoxicity assay were performed and compared between the RENCA rechallenge group after either excision or cryoablation (Fig. 1).

Bottom Line: The mice successfully treated were rechallenged with RENCA or an undifferentiated colon carcinoma cell line, CT26, in the contralateral right flank area.The cryoablation group showed an elevated CD3, CD4, CD8 T, and natural killer cell count in the FACS analysis and also showed significantly increased cytotoxicity in the (51)Cr release assay compared with the excision group.These results showed that cryoablation, compared to surgical resection, was more effective in preventing tumor growth after rechallenge with RENCA cells and that this response was tumor-specific, because the CT26 cells did not have the same effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Korea University Anam Hospital, Seoul, Korea.

ABSTRACT

Purpose: To evaluate tumor-specific immunity and define the mechanisms involved in the cryoimmunologic response, we compared the tumor control efficacy and immunologic responses of cryoablation with those of surgical excision in a tumor rechallenge model.

Materials and methods: Sixty BALB/c mice with RENCA tumors that were generated in the left flank area underwent cryoablation or radical excision. The mice successfully treated were rechallenged with RENCA or an undifferentiated colon carcinoma cell line, CT26, in the contralateral right flank area. The recurrence rate after tumor rechallenge in each group was then observed. To assess the immunologic response of each treatment modality, fluorescent-activated cell sorting (FACS) analysis and a cytotoxicity assay using (51)Cr release were performed.

Results: After reinoculation of the RENCA cells, the rate of tumor growth was significantly higher in the surgical excision group than in the cryoablation group (94.4% vs. 11.1%, p=0.001). In the cryoablation group, the tumor growth rate was significantly increased after rechallenge of CT26 cells compared with RENCA (94.1% vs. 11.1%, p=0.001). The cryoablation group showed an elevated CD3, CD4, CD8 T, and natural killer cell count in the FACS analysis and also showed significantly increased cytotoxicity in the (51)Cr release assay compared with the excision group.

Conclusions: These results showed that cryoablation, compared to surgical resection, was more effective in preventing tumor growth after rechallenge with RENCA cells and that this response was tumor-specific, because the CT26 cells did not have the same effect.

Show MeSH
Related in: MedlinePlus