Dr. Weeks’ Comment: I’m grateful to my empowered and motivated clients like Brian who routinely scan the web for relevant articles and share them with me. Here is an impressive treatment which enhances immune response while killing cancer TUMOR cells. Still, per the principles of Corrective Cancer Care™, this cryoablation procedure REQUIRES the concurrent use of SOUL or CORE or any safe and powerful anti-inflammatory agent so that the IL-6 inflammatory cytokine SOS message (which is part of the natural healing response does not attract new uncommitted cancer STEM cells which, upon arrival at the site of injury (cryoablation) would create more liver cancer STEM cells) in snuffed and the typical harm created by chemo and radiation does NOT occur. Confused by that biochemistry? Read this or Watch this.
Cryoablation-Induced Anti-Cancer Immune Reaction
Shinji Osada*, Hisashi Imai, Yoshiyuki Sasaki and Kazuhiro Yoshida
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Abstract
Ablative techniques have been developed against advanced liver cancer in cases where surgical resection is impossible. Among the ablation procedures used, thermal ablation therapy is widely applied, and the safety and efficacy of this technique have been well characterized to control local progression of cancer. However the principle of cryosurgery is not only to control local recurrence, but also to stimulate the immune system into initiating an anti-tumor response. In recent years, we have used a liquid nitrogen-based cryogenic procedure and developed a treatment method for patients with unresectable liver tumors. Following this, repeated treatment was demonstrated to induce anticancer immune reaction-related factors. In the present study, a novel strategy of a cryoablation-induced anti-cancer immune reaction will be introduced.
Hepatic resection has been the only curative option for patients with liver tumors. However, due to limited hepatic reserves, high surgical risk, or unfavorable tumor location, surgery is not always possible [1,2], therefore several ablative techniques, based on chemical (percutaneous ethanol injection), cold-based (cryotherapy), or heatbased (radiofrequency ablation; RFA, microwave coagulation therapy; MCT), have been developed [3]. Among these procedures, thermal ablation therapy [4,5] and cryotherapy [6] have been commonly used in worldwide, and the safety and efficacy of this technique have been well characterized. According to a recent comparative study, while similar success and complication rates were found, local recurrence is more frequent in cryotherapy [7]. However, the principle of cryosurgery is not only to facilitate a low recurrence rate, but also due destruction of tissue intracellular antigens that are released into the circulation enable cryogenic treatment to stimulate the immune system for an anti-tumor response [6,8]. In the present report, a novel strategy with a cryoablation-induced anti-cancer immune reaction will be introduced.
Ablation therapy for local cancer progression
Among several procedures to treat hepatic tumors, RFA is one of the most convenient and reliable regional therapies used to prolong patient survival. A worldwide study demonstrated the complication and mortality rates at 8.9% and 0.5%, respectively [9], and post treatment imaging showed complete avascularity if the tumor diameter was smaller than 3cm [10]. In contrast, the main effect of cryoablation is based on intra and extracellular ice formation and the intracellular ice formation causes injury of intracellular structures, membrane rupture, osmotic dehydration, anoxia and finally cell death [11]. During cryoablation the interface of the frozen/unfrozen liver can be assessed easily with intra-operative ultrasound by the appearance of an echogenic edge with posterior acoustic shadowing, and this is a major advantage of cryoablation over RFA (described later). Morbidity and mortality rates after cryosurgery were demonstrated as being higher than thermal ablation, ranging from 8 to 41% and around 20%, respectively [12]. Among the complications, the phenomenon of cryoshock is responsible for the majority of all mortality. Due to this rare (1%) but severe complication, cryoablation is recognized as a problematic treatment.
Larger tumor size increases the risk of complications and also of local recurrence. In a comparative study, a significantly higher local recurrence rate (38% vs. 17%) was reported for large tumors, diameter over 3cm, but not for small tumor, when RFA was compared with cryo-therapy [7]. Then, RFA is now evaluated as the most favorable procedure among ablation therapies from its safety and certainty, but there are still limits in its usage due to tumor size and location [13].
Significances in immune reaction for cancer progression
Two subtypes of T-helper cells were found to have differences in cytokine secretion pattern and other functions, which indicated that Th1 and Th2 cells were important regulators of immune response. Th1 cells are hypothesized to lead the attack against intracellular pathogens such as viruses, raise the classic delayed-type hypersensitivity skin response to viral and bacterial antigens, and fight cancer cells. Th2 cells are believed to emphasize protection against extracellular pathogens such as multicellular parasites. More recently, a new subset of helper T-cells, called Th17, was reported as being related to the autoimmune diseases [14]. Th1, Th2 and Th17 subsets are produced from a noncommitted population of precursor naïve T cells (Figure 1). As they attain maturity, Th1 cells also produce IFN-gamma, TNF-alpha, and IL-2. Like the Th1 cells, the emergence of Th2 cells is also dependent on their cytokine environment, such as IL-4 from an APC. In addition, for Th17 cells, IL-6 or TGF-beta is important.
The development of an immune microenvironment for tumor tolerance is achieved through a variety of immune-suppressive mechanisms, and subsequently subverts the immune system away from tumor recognition and rejection [15,16]. During the process of immune suppression, malignant tumor progression can be associated with a general shift in Th1/Th2 immune response; Th1 cytokines are typically lower, while the Th2 marker can be higher or unchanged. Th2 reaction has a variety of suppressive effects for Th1 cytokine production and suppresses killer cells activity. In contrast, IL-12 is another cytokine that can be up-regulated by Th1 activity and subsequently, the Th1/Th2 ratio was found to be important in cervical cancer patients [17]. The macrophages associated with developing solid tumors have a phenotype that is also driven primarily by Th2 cytokines and supports a pro-tumor microenvironment [18].
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