Resistance to tumour challenge after tumour laser thermotherapy is associated with a cellular immune response

Abstract

Previous studies in our laboratory have shown that interstitial laser thermotherapy (ILT) of an experimental liver tumour is superior to surgical excision, at least partly due to a laser-induced immunological effect. The aim of the present study was to investigate the time -response relationship of the ILT-induced immunisation and the cellular response of macrophages and lymphocytes. A dimethylhydrazine-induced adenocarcinoma was transplanted into the liver of syngeneic rats. Rats with tumour were treated 6 -8 days later (tumour size 0.25 -0.40 cm 3 ) with ILT of tumour or resection of the tumour-bearing lobe. Two groups of rats without tumour were treated with resection of a normal liver lobe or ILT of normal liver. A challenging tumour was implanted into the liver of each rat 2, 5 or 10 weeks after primary treatment. Rats were killed 6, 12 and 48 days (or earlier due to their condition) after challenge (n ¼ 8 in all groups). Immunohistochemical techniques were used to determine lymphocytes (CD8, CD4) and macrophages (ED1, ED2) in rats having had treatment of a primary tumour. Interstitial laser thermotherapy of the first tumour was followed by eradication of challenging tumour and absence of tumour spread. This contrasted with rapid growth and spread of challenging tumour in the other groups. In the challenging vital tumour tissue and in the interface between the tumour and surroundings, the number of ED1 macrophages and CD8 lymphocytes was higher in rats having been treated with the ILT of tumour than in those having undergone resection of the tumour-bearing lobe. The number of ED2 macrophages and CD4 lymphocytes was low and did not vary between these two groups. Interstitial laser thermotherapy elicited an immune response that eradicated a challenging tumour and was associated with increased numbers of tumour-infiltrating macrophages and CD8 lymphocytes.

Radiofrequency ablation of colorectal liver metastases induces an inflammatory response in distant hepatic metastases but not in local accelerated outgrowth

“…Many studies have been performed showing that local ablative therapies induce an inflammatory response [14,15,[23][24][25]. In this study we show that the inflammatory reaction induced by RFA is primarily observed in distant hepatic metastases, but not in perinecrotic Journal of Surgical Oncology Fig.…”

Unmasking of α-Fetoprotein-Specific CD4+ T Cell Responses in Hepatocellular Carcinoma Patients Undergoing Embolization

“…The identification of a population of AFP-specific CD4 ϩ T cells during therapy that are not detectable in treatmentnaive patients could be explained by work showing that necrotic cells induce a different set of class II peptides than cells dying via apoptosis (36). In animal tumor models, an in situ vaccination effect has also been proposed to occur after photodynamic therapy, interstitial laser thermotherapy, and radiofrequency ablation, all of which produce necrosis of tumors (35,37,38). Those studies demonstrated treatment-induced generation of a protective tumor-specific T cell response to tumor rechallenge.…”

Immunological Consequences of Nanoparticle‐Mediated Antitumor Photoimmunotherapy

“…Many of PSs that have been studied so far include, but not limited to porphyrins, porphyrin analogs chlorines, phthalocyanines, indocyanines, and other agents with suitable photophysical properties . On the other hand, PTT uses a photoabsorbing agent to convert light into heat, leading to the thermal ablation of cancer cells . In addition to the direct apoptosis and necrosis by light, phototherapies have been well‐known to elicit antitumor immune responses by producing an acute inflammatory response which ultimately activates the production of proinflammatory cytokines and leukocyte infiltration to regulate TME ( Figure ) .…”