Open Access

Thermal ablation in cancer (Review)

  • Authors:
    • Yong Liu
    • Cheng-Song Cao
    • Yang Yu
    • Ya-Meng Si
  • View Affiliations

  • Published online on: August 11, 2016     https://doi.org/10.3892/ol.2016.4997
  • Pages: 2293-2295
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Radiofrequency ablation (RFA) and cryo­ablation are alternative forms of therapy used widely in various pathological states, including treatment of carcinogenesis. The reason is that ablation techniques have ability of modulating the immune system. Furthermore, recent studies have applied this form of therapy on tumor microenvironment and in the systematic circulation. Moreover, RFA and cryoablation result in an inflammatory immune response along with tissue disruption. Evidence has demonstrated that these procedures affect carcinogenesis by causing a significant local inflammatory response leading to an immunogenic gene signature. The present review enlightens the current view of these techniques in cancer.

Introduction

Interventional procedures involving exposure to extreme temperatures to cause local tissue damage are termed as thermal ablation (1). The two most commonly used procedures that comprise thermal ablation, are radiofrequency ablation (RFA) and cryoablation. The two procedures involve the introduction of a metal probe using ultrasound or computed tomography (CT) guidance as a visual aid. Small tumors are usually destroyed by exposing them to two different temperature extremes, high burning temperature via RFA and freezing tissue cold temperature via cryoablation.

In terms of local treatment strategies, cryoablation is an attractive treatment modality as it is safe and effective in the treatment of kidney, liver, bone, lung, adrenal and soft tissue masses (2,3). Furthermore, it is palliative in nature as the freezing procedure causes a local analgesic effect. Cost effectiveness is another positive aspect of cryoablation. Additionally, cryosurgery is another ablation method showing progress in prostate and breast cancer subjects and has thus become a widely applied technique in research for both immunologists and oncologists (2,3).

Cryoablation and cancer

Cryoablation has been reported to induce microvascular thrombosis, membrane disruption, solution effects, ice crystallization and organelle disruption in cancer cells (4). These differentially induced processes affect cells variably and eventually result in apoptosis or even necrotic cell death (5). Reiter et al observed that cryotherapy was more effective in exerting an antitumor effect by virtue of cell necrosis as compared to ultraviolet (UV)-induced apoptosis in bone marrow-derived murine macrophage (6). Sauter et al evidenced the specificity of cryotherapy by inducing necrosis on immature dendritic cells (DCs) as they have ability to induce apoptosis and necrosis (7).

Previous studies have focused on the nature of cryotherapy-induced immune effects, i.e., immunosuppressive or immune-stimulatory. The ‘danger’ theory suggested the immune system is capable of recognizing any cell injury as a threat, thereby inducing responses. This is termed immune-stimulatory (8). Similarly, cryotherapy-induced necrosis is immune-stimulatory in nature as it leads to the denaturing of proteins or cell wall breakdown. Immune stimulation during cryotherapy is visible in the form of high mobility group box 1 (HMGB1) inflammatory factor, uric acid, and heat shock proteins (HSPs), including hsp70 and hsp90 (9). On the other hand, apoptosis is immune suppressive in nature and unable to release HMGB1 (10). Scheffer et al studied protective attributes of the two processes and observed that apoptotic cells induced significant protection and prolonged survival, while necrotic cell vaccine provided little protection (11). Conversely, Kotera et al found pulsing DCs with apoptotic cells produced by UVB exposure showed immune-stimulatory effects (12). Gamrekelashvili et al used ganciclovir to induce tumor cell apoptosis and a vascular targeting drug, ZD6126, to process necrotic tumor cells, thereby observing both immune-stimulatory as well as immune-suppressive effects (13). Feng et al also observed both these effects in leukemic cells (14). Therefore, the induction of necrotic and apoptotic cells is important in the generation of an immune-reactive or immunosuppressive response and cryosurgery is an important contributor to the management of carcinogenesis.

Surgical diathermy

Kolicher for the first time evidenced the efficacy of surgical diathermy during cancer in 1910 (15). The key player in this form of therapy was observed to be the reticuloendothelial system. In surgical diathermy, RFA is often utilized for therapeutic exposures. McGahan et al demonstrated the local effects of RFA via ultrasound including necrosis, hemorrhage and congestion in swine models (16). RFA was reported to cause statistically significant infiltration of T cells in a hepatoma model in rabbits (17). Additionally, in the combination approach, RFA together with CTLA4 was reported to be more effective against tumor and proved successful in the enhancement of survival (18).

RFA and its associated effects

RFA resulted in T-cell response together with the infiltration of DCs within tumors in a murine urothelial carcinoma model (19). In humans, RFA has been reported to be effective in metastatic liver tumors during hepatocellular carcinoma (HCC) (20). In an additional study, RFA promoted the release of interferon (IFN)-γ following the procedure (21). In another study, in 20 patients with localized HCC unfit for liver transplantation or surgical resection, RFA proved beneficial by promoting the frequency of circulation of IFN-γ-positive cells (22). Zerbini et al showed that RFA is also capable of inducing maturation of antigen-presenting cells (APCs) capable of producing specific T cells for HCC (23).

Cryosurgery in cancer

The approach of cryosurgery has also been reported to have an immune-stimulatory and immunosuppressive nature (24). Myers et al used mouse models for fibrosarcoma and mammary tumors to observe the effectiveness of cryosurgery (25). Using a rat model, Blackwood and Cooper found that animals who received cryoablation for myosarcoma and carcinosarcoma cell line-derived tumors were protected against intraperitoneal implantation (26). Neel et al also compared surgical approach and cryoablation in mice with virally-induced mammary adenocarcinoma or chemically-induced sarcoma. The results of that study showed that cryoablation was more efficient in improving survival time after tumor rechallenge (27).

Mechanism behind cryosurgery/RFA

The in vivo melanoma mouse model was utilized to determine mechanisms underlying cryosurgery, RFA and tumor vaccination. RFA and cryosurgery appeared to produce an in situ depot of tumor antigen and debris. These approaches have been observed to cause an increase in immature DCs within tumor draining lymph nodes that ultimately cause tumor invasion. Furthermore, as discussed earlier, the combination therapy was more beneficial and effective through the addition of anti-CTLA4 to any thermal ablation approach, whether. cryosurgery or RFA (18). It has also been suggested in the literature that these approaches result in an increased ratio of effector CD8 T cells compared to T-regulatory cells, thereby resulting in a systemic specific immunity.

Conclusion

Based on the above literature it can be concluded that thermal ablation procedures affect carcinogenesis by causing a significant local inflammatory response leading to an immunogenic gene signature. However, additional studies are required to clinically confirm the outcomes and to make it a gold standard therapy for the management of cancer patients.

Acknowledgements

The present study is supported by the Six Major Talent Peak Project no. 2014-WSW-065 and the Wu Jieping Foundation for Clinical Research of Medical Science Foundation no. 320.6750.15255.

References

1 

Voigt JD and Barnett G: The value of using a brain laser interstitial thermal therapy (LITT) system in patients presenting with high grade gliomas where maximal safe resection may not be feasible. Cost Eff Resour Alloc. 14:62016. View Article : Google Scholar : PubMed/NCBI

2 

Alblin RJ, Soanes WA and Gonder MJ: Prospects for cryo-immunotherapy in cases of metastasizing carcinoma of the prostate. Cryobiology. 8:271–279. 1971. View Article : Google Scholar : PubMed/NCBI

3 

Suzuki Y: Cryosurgical treatment of advanced breast cancer and cryoimmunological responses. Skin Cancer. 10:19–26. 1995.

4 

Sabel MS: Cryo-immunology: a review of the literature and proposed mechanisms for stimulatory versus suppressive immune responses. Cryobiology. 58:1–11. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Gallucci S, Lolkema M and Matzinger P: Natural adjuvants: endogenous activators of dendritic cells. Nat Med. 5:1249–1255. 1999. View Article : Google Scholar : PubMed/NCBI

6 

Reiter I, Krammer B and Schwamberger G: Cutting edge: differential effect of apoptotic versus necrotic tumor cells on macrophage antitumor activities. J Immunol. 163:1730–1732. 1999.PubMed/NCBI

7 

Sauter B, Albert ML, Francisco L, Larsson M, Somersan S and Bhardwaj N: Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med. 191:423–434. 2000. View Article : Google Scholar : PubMed/NCBI

8 

Matzinger P: Tolerance, danger, and the extended family. Annu Rev Immunol. 12:991–1045. 1994. View Article : Google Scholar : PubMed/NCBI

9 

Shi Y, Evans JE and Rock KL: Molecular identification of a danger signal that alerts the immune system to dying cells. Nature. 425:516–521. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Scaffidi P, Misteli T and Bianchi ME: Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 418:191–195. 2002. View Article : Google Scholar : PubMed/NCBI

11 

Scheffer SR Sr, Nave H, Korangy F, Schlote K, Pabst R, Jaffee EM, Manns MP and Greten TF: Apoptotic, but not necrotic, tumor cell vaccines induce a potent immune response in vivo. Int J Cancer. 103:205–211. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Kotera Y, Shimizu K and Mulé JJ: Comparative analysis of necrotic and apoptotic tumor cells as a source of antigen(s) in dendritic cell-based immunization. Cancer Res. 61:8105–8109. 2001.PubMed/NCBI

13 

Gamrekelashvili J, Krüger C, von Wasielewski R, Hoffmann M, Huster KM, Busch DH, Manns MP, Korangy F and Greten TF: Necrotic tumor cell death in vivo impairs tumor-specific immune responses. J Immunol. 178:1573–1580. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Feng H, Zeng Y, Graner MW and Katsanis E: Stressed apoptotic tumor cells stimulate dendritic cells and induce specific cytotoxic T cells. Blood. 100:4108–4115. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Kolischer G: Surgical diathermy in malignancy. Am J Surg. 7:249–250. 1929. View Article : Google Scholar

16 

McGahan JP, Brock JM, Tesluk H, Gu WZ, Schneider P and Browning PD: Hepatic ablation with use of radio-frequency electrocautery in the animal model. J Vasc Interv Radiol. 3:291–297. 1992. View Article : Google Scholar : PubMed/NCBI

17 

Wissniowski TT, Hänsler J, Neureiter D, Frieser M, Schaber S, Esslinger B, Voll R, Strobel D, Hahn EG and Schuppan D: Activation of tumor-specific T lymphocytes by radio-frequency ablation of the VX2 hepatoma in rabbits. Cancer Res. 63:6496–6500. 2003.PubMed/NCBI

18 

denBrok MH, Sutmuller RP, van der Voort R, Bennink EJ, Figdor CG, Ruers TJ and Adema GJ: In situ tumor ablation creates an antigen source for the generation of antitumor immunity. Cancer Res. 64:4024–4029. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Dromi SA, Walsh MP, Herby S, Traughber B, Xie J, Sharma KV, Sekhar KP, Luk A, Liewehr DJ, Dreher MR, et al: Radiofrequency ablation induces antigen-presenting cell infiltration and amplification of weak tumor-induced immunity. Radiology. 251:58–66. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Napoletano C, Taurino F, Biffoni M, De Majo A, Coscarella G, Bellati F, Rahimi H, Pauselli S, Pellicciotta I, Burchell JM, et al: RFA strongly modulates the immune system and anti-tumor immune responses in metastatic liver patients. Int J Oncol. 32:481–490. 2008.PubMed/NCBI

21 

Hansler J, Wissniowski TT, Schuppan D, Witte A, Bernatik T, Hahn EG and Strobel D: Activation and dramatically increased cytolytic activity of tumor specific T lymphocytes after radio-frequency ablation in patients with hepatocellular carcinoma and colorectal liver metastases. World J Gastroenterol. 12:3716–3721. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Zerbini A, Pilli M, Penna A, Pelosi G, Schianchi C, Molinari A, Schivazappa S, Zibera C, Fagnoni FF, Ferrari C, et al: Radiofrequency thermal ablation of hepatocellular carcinoma liver nodules can activate and enhance tumor-specific T-cell responses. Cancer Res. 66:1139–1146. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Zerbini A, Pilli M, Fagnoni F, Pelosi G, Pizzi MG, Schivazappa S, Laccabue D, Cavallo C, Schianchi C, Ferrari C, et al: Increased immunostimulatory activity conferred to antigen-presenting cells by exposure to antigen extract from hepatocellular carcinoma after radiofrequency thermal ablation. J Immunother. 31:271–282. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Sidana A, Chowdhury WH, Fuchs EJ and Rodriguez R: Cryoimmunotherapy in urologic oncology. Urology. 75:1009–1014. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Myers RS, Hammond WG and Ketcham AS: Tumor-specific transplantation immunity after cryosurgery. J Surg Oncol. 1:241–246. 1969. View Article : Google Scholar : PubMed/NCBI

26 

Blackwood CE and Cooper IS: Response of experimental tumor systems to cryosurgery. Cryobiology. 9:508–515. 1972. View Article : Google Scholar : PubMed/NCBI

27 

Neel HB III, Ketcham AS and Hammond WG: Experimental evaluation of in situ oncocide for primary tumor therapy: comparison of tumor-specific immunity after complete excision, cryonecrosis and ligation. Laryngoscope. 83:376–387. 1973. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

October-2016
Volume 12 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Liu Y, Cao C, Yu Y and Si Y: Thermal ablation in cancer (Review). Oncol Lett 12: 2293-2295, 2016
APA
Liu, Y., Cao, C., Yu, Y., & Si, Y. (2016). Thermal ablation in cancer (Review). Oncology Letters, 12, 2293-2295. https://doi.org/10.3892/ol.2016.4997
MLA
Liu, Y., Cao, C., Yu, Y., Si, Y."Thermal ablation in cancer (Review)". Oncology Letters 12.4 (2016): 2293-2295.
Chicago
Liu, Y., Cao, C., Yu, Y., Si, Y."Thermal ablation in cancer (Review)". Oncology Letters 12, no. 4 (2016): 2293-2295. https://doi.org/10.3892/ol.2016.4997