Serum cytokine levels in response to hepatic cryoablation

Osada, Shinji; Imai, Hisashi; Tomita, Hiroyuki; Tokuyama, Yasuharu; Okumura, Naoki; Matsuhashi, Nobuhisa; Sakashita, Fumio; Nonaka, Kenichi

doi:10.1002/jso.20712

Cited by 57 publications

(46 citation statements)

References 27 publications

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“…27 So far, cytokine levels in serum of patients with breast cancer after cryoablation has not been reported, but in patients with prostate cancer it was found that IFNg and TNFa significantly increased after cryoablation in the serum, 28 while in patients with hepatic cancer TNFa and IL-10 increased significantly in the serum after cryoablation. 29 In summary, these results indicate that the production of cytokines for each cancer may be different and should be analyzed for each individual patient to develop a personalized combination therapy. Based on patient's cytokine profile, an optimal adjuvant could be selected for combining with cryoablation.…”

Section: Discussionmentioning

confidence: 96%

Cryoablation and Meriva have strong therapeutic effect on triple-negative breast cancer

et al. 2015

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Keywords: adjuvant, cryoablation, immunogenic tumor cell death, Mage-b, Meriva, metastatic breast cancer, Survivin, triple-negative breast cancer, vaccinesInterleukin-6, a cytokine produced particularly by triple-negative breast cancers, strongly inhibits T cell responses in the tumor microenvironment. Here we tested cryoablation combined with Meriva (a lecithin delivery system of curcumin with improved bioavailability) in mice with metastatic breast cancer (4T1). Cryoablation involves killing of tumor cells through freezing and thawing, resulting in recruitment of tumor-specific T cells, while curcumin stimulates T cells through the reduction of IL-6 in the TME. Cryoablation plus Meriva accumulated and activated CD8C T cells to multiple tumor-associated antigens such as Mage-b and Survivin (both expressed by 4T1 tumors). This correlated with a nearly complete reduction of 4T1 primary tumors and lung metastases while little effect was observed from saline or Meriva alone (28 d after tumor cell injection). The survival rate in the group of cryoablation plus Meriva was significantly improved compared to all control groups. Using a less aggressive 4T1 model expressing luciferase (4T1.2luc3), we demonstrated that all mice receiving saline or Meriva developed metastases in the lungs and a primary tumor (38 d after tumor cell injection; and died soon after that), but not the mice receiving cryoablation or cryoablation plus Meriva. However, on day 58 the mice receiving cryoablation developed 4T1.2luc3 metastases in the lungs, while mice receiving cryoablation plus Meriva were free of metastases. These results strongly suggest that cryoablation delayed the development of lung metastases on the short-term, but Meriva administered after cryoablation was significantly better in delaying the development of lung metastases and survival on the long-term.

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Section: Discussionmentioning

confidence: 96%

Cryoablation and Meriva have strong therapeutic effect on triple-negative breast cancer

et al. 2015

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“…Recent studies have examined the outcomes of percutaneous cryoRx for HCC using CT monitoring and MR guidance, reporting that it is safe and efficacious (30). Moreover, it was found that not only was the local tumor necrotic, but also that the adjacent tumor tissue was necrotic and shrunken in HCC patients following cryoRx, which was regarded as reflecting ectopic tumor suppression (16). We report that following cryoablation for small HCC the 1-, 2-and 3-year recurrence-free survival rates were 72, 56 and 43%, respectively (25).…”

Section: Discussionmentioning

confidence: 99%

“…Although the value of cryotherapy (cryoRx) in HCC is not yet as well established as that of RFA, cryoRx has been found to be more advantageous for improving immunity following treatment compared to RFA. Osada et al found that not only the local tumor, but also the adjacent tumor tissue was necrotic and shrunken in HCC patients following cryoablation, which was regarded as ectopic tumor suppression (16). This response may be associated with the release of tumor antigens, resulting in the host production of anti-tumor antibodies (17).…”

Section: Introductionmentioning

confidence: 99%

Cryotherapy is associated with improved clinical outcomes of sorafenib for the treatment of advanced hepatocellular carcinoma

Yang

Wang

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Sorafenib may prolong survival in patients with advanced hepatocellular carcinoma (HCC), but with limited efficacy. The present study aimed to assess the safety and efficacy of sorafenib combined with cryotherapy (cryoRx) for the treatment of advanced HCC. A total of 104 patients met the following criteria: advanced HCC without distant metastasis, presence of portal vein thrombosis, Child-Pugh class A or B and life expectancy of at least 12 weeks. All patients were randomly assigned to sorafenib and cryoRx (n=52) or sorafenib-alone (n=52) treatment groups. The primary end-point of the study was overall survival (OS). The secondary end-points included time to progression (TTP) and tolerability. Microvessel density (MVD) was assessed following immunostaining for CD34. In a median of 10.5 (4-26) months follow-up, the median OS was 12.5 months (95% CI 10.6-16.4) in the combination therapy vs. 8.6 months (7.3-10.4) in the sorafenib-alone (P= 0.01) group. The median TTP was 9.5 months (8.4-13.5) in the combination therapy vs. 5.3 months (3.8-6.9) in the sorafenib alone (P=0.02) group. CryoRx was an independent factor associated with improved clinical outcomes of sorafenib for the treatment of advanced HCC. Patients with low intratumoral MVD receiving the combination therapy exhibited a significantly longer median TTP and OS compared to those receiving sorafenib. High intratumoral MVD was an independent predictor of poor responses to sorafenib for advanced HCC. Compared with previous reports of sorafenib-related adverse drug reactions (ADRs), cryoRx did not further increase the frequency and degree of sorafenib-related ADRs. In conclusion, compared to sorafenib alone, the addition of cryoRx to sorafenib significantly improves the clinical outcomes of sorafenib for the treatment of advanced HCC with acceptable tolerance and similar safety profiles as previously reported. High intratumoral MVD is predictive of poor responses to sorafenib in advanced HCC patients.

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“…125 The results also demonstrate that immunogenic TAAs remain available in the tumor debris after HIFU ablation for effective presentation by DCs, increasing the number and activity of TILs. 126 …”

Section: Physical Treatmentsmentioning

confidence: 99%

“…Recent clinical studies revealed the upregulation of serum cytokine levels and generation of tumor-specific T-cells following cryoablation. 126,127 The simplicity of cryoablation coupled with its minimal negative effects on the immune system make this procedure an attractive candidate for combination regiment with immunotherapy. 124 Chemotherapy Long-standing dogma suggested that myelosuppressive effects of chemotherapy would prevent its application in combination with immunotherapy.…”

Section: Cryoablationmentioning

confidence: 99%

Clinically feasible approaches to potentiating cancer cell-based immunotherapies

Селедцов

Гончаров

Селедцова

2015

Human Vaccines & Immunotherapeutics

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Serum cytokine levels in response to hepatic cryoablation

Abstract: It might be possible to evaluate the appearance of immune responses to cryosurgery by monitoring serum cytokine levels.

Cited by 57 publications

References 27 publications

Cryoablation and Meriva have strong therapeutic effect on triple-negative breast cancer

Cryoablation and Meriva have strong therapeutic effect on triple-negative breast cancer

Cryotherapy is associated with improved clinical outcomes of sorafenib for the treatment of advanced hepatocellular carcinoma

Clinically feasible approaches to potentiating cancer cell-based immunotherapies

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