Changes in immunocompetent cells after interstitial laser thermotherapy of breast cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.BACKGROUND: Local tumour destruction has been shown to give rise to changes in immunocompetent cells. The aim of this study was to describe the effect of interstitial laser thermotherapy (ILT) of breast carcinoma in the tumour and in regional lymph nodes. METHODS: Seventeen women that underwent radical surgical excision after non-radical ILT were studied. ILT was performed at a steady-state temperature of 48°C for 30 min. Surgical excision was performed 12 (6-23) days after ILT. Six patients with breast cancer not treated with ILT before surgery served as controls. Immunohistological reactions were performed on core needle biopsies prior to treatment and on the excised specimens. RESULTS: ILT resulted in more CD8 lymphocytes and CD68 macrophages within the tumour (P < 0.05 and P < 0.01, respectively) and higher counts of CD20 (P < 0.05), CD68 (P < 0.001) and CD83 (P < 0.01) at the tumour border, when compared to pre-treatment values. In the control patients not receiving ILT, CD8 cells increased within the tumour after resection (P < 0.05). With the probable exception of CD25 Foxp3 cells, the presence of cancer in a lymph node influenced the findings in lymph nodes (examined for CD1a, CD25, Foxp3 CD25, CD83 cells). Thus, comparisons between ILT and control patients were restricted to patients without lymph node metastases. In these patients, ILT and resection were followed by a decrease in CD25 Foxp3 lymphocytes (P < 0.05), when compared to surgical resection alone. CONCLUSIONS: ILT induced changes in immunocompetent cells in patients with breast cancer. The stimulation of the immune system is an added feature of ILT in treatment of patients with breast cancer

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

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 = 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

Heat shock protein 70 (HSP70) after laser thermotherapy of an adenocarcinoma transplanted into rat liver.

The heat shock proteins (HSPs) HSP70 and gp96 from necrotic tumour cells are considered to function as chaperones in presenting tumour antigens. We therefore studied HSP70 and immune cells in a transplantable carcinoma in the liver of rats after interstitial laser thermotherapy (ILT). Experiments were performed in Wistar FU rats using a dimethyl-hydrazine-induced adenocarcinoma implanted into the left lateral lobe of the liver. Rats were randomized to one of the following groups: a) ILT of tumour, b) sham ILT, or c) control. ILT was suboptimal and was performed at a steady-state temperature of 43 degrees C at the tumour margin for 30 minutes. Rats were killed 15 minutes, 5 hours, 10 hours, 15 hours or 12 days after treatment. Double immunohistochemistry was performed for HSP70 and ED1 macrophages or CD8 lymphocytes, and ELISA for serum concentrations of HSP70. After ILT, there was an increase of HSP70 immunoreactivity in tumours as compared to sham ILT. At the same time, tumour cells affected by ILT showed a shift of HSP70 from the cytoplasm to the nucleus with a peak at 10 hours. Few CD8-positive cells were found. There was an increase of tumour-infiltrating ED1 macrophages after ILT as compared to sham ILT at 10-15 hours after treatment. HSP70 was present in ED1 macrophages significantly more frequently after ILT than after sham ILT, and this was true both for HSP70 localized to the surface and the cytoplasm of the macrophage. There was a significant increase in serum HSP70 during the first 15 hours after ILT. In conclusion, laser thermotherapy resulted in increased HSP70 immunoreactivity within tumours and HSP70 shifts from cytoplasm to nucleus. Furthermore, it resulted in increased numbers of tumour-infiltrating macrophages and an increased presence of HSP70 in the membrane and cytoplasm of these macrophages