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

K Ivarsson, L Myllymäki, K Jansner, U Stenram, K-G Tranberg, K Ivarsson, L Myllymäki, K Jansner, U Stenram, K-G Tranberg

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 = 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.

Figures

Figure 1
Figure 1
Schematic illustration of feedback temperature system for ILT. ATS, automatic thermometry system; PC, personal computer.
Figure 2
Figure 2
Immunohistochemical findings 12 days after rechallenge following ILT (group I). (A) Fibrotic remnants of tumour in the upper half, liver tissue in the lower half. Brown colour indicates ED1 macrophages. Black bar: 50 μm. (B) Vital tumour from another animal, in the upper third of the photo, liver tissue in the lower half. Brown colour indicates CD8 lymphocytes. Black bar: 50 μm.

References

    1. Barba D, Hardin J, Sadelain M, Gage FH (1994) Development of anti-tumor immunity following thymidine kinase-mediated killing of experimental brain tumors. Proc Natl Acad Sci USA 91: 4348–4352
    1. Basu S, Binder RJ, Suto R, Anderson KM, Srivastava PK (2000) Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappaB pathway. Int Immunol 12: 1539–1546
    1. Carlsson G, Gullberg B, Hafström L (1983) Estimation of liver tumor volume using different formulas: an experimental study in rats. J Cancer Res Clin Oncol 105: 20–23
    1. Caruso M, Panis Y, Gagandeep S, Houssin D, Salzmann JL, Klatzmann D (1993) Regression of established macroscopic liver metastases after in situ transduction of a suicide gene. Proc Natl Acad Sci USA 90: 7024–7028
    1. Chen WR, Adams RL, Carubelli R, Nordquist RE (1997) Laser-photosensitizer assisted immunotherapy: a novel modality for cancer treatment. Cancer Lett 115: 25–30
    1. Chen WR, Zhu WG, Dynlacht JR, Liu H, Nordquist RE (1999) Long-term tumor resistance induced by laser photo-immunotherapy. Int J Cancer 81: 808–812
    1. Consalvo M, Mullen CA, Modesti A, Musiani P, Allione A, Cavallo F, Giovarelli M, Forni G (1995) 5-Fluorocytosine-induced eradication of murine adenocarcinomas engineered to express the cytosine deaminase suicide gene requires host immune competence and leaves an efficient memory. J Immunol 154: 5302–5312
    1. Cummings MC, Winterford CM, Walker NI (1997) Apoptosis (see comments). Am J Surg Pathol 21: 88–101
    1. Damoiseaux JG, Dopp EA, Calame W, Chao D, MacPherson GG, Dijkstra CD (1994) Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1. Immunology 83: 140–147
    1. Dijkstra CD, Dopp EA, Joling P, Kraal G (1985) The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. Immunology 54: 589–599
    1. Dranoff G (2004) Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer 4: 11–22
    1. Ganss R, Ryschich E, Klar E, Arnold B, Hammerling GJ (2002) Combination of T-cell therapy and trigger of inflammation induces remodeling of the vasculature and tumor eradication. Cancer Res 62: 1462–1470
    1. Horiguchi S, Petersson M, Nakazawa T, Kanda M, Zea AH, Ochoa AC, Kiessling R (1999) Primary chemically induced tumors induce profound immunosuppression concomitant with apoptosis and alterations in signal transduction in T cells and NK cells. Cancer Res 59: 2950–2956
    1. Isbert C, Boerner A, Ritz JP, Schuppan D, Buhr HJ, Germer CT (2002) In situ ablation of experimental liver metastases delays and reduces residual intrahepatic tumour growth and peritoneal tumour spread compared with hepatic resection. Br J Surg 89: 1252–1259
    1. Ivarsson K, Myllymaki L, Jansner K, Bruun A, Stenram U, Tranberg KG (2003) Heat shock protein 70 (HSP70) after laser thermotherapy of an adenocarcinoma transplanted into rat liver. Anticancer Res 23: 3703–3712
    1. Kuriyama S, Kikukawa M, Masui K, Okuda H, Nakatani T, Akahane T, Mitoro A, Tominaga K, Tsujinoue H, Yoshiji H, Okamoto S, Fukui H, Ikenaka K (1999a) Cancer gene therapy with HSV-tk/GCV system depends on T-cell-mediated immune responses and causes apoptotic death of tumor cells in vivo. Int J Cancer 83: 374–380
    1. Kuriyama S, Kikukawa M, Masui K, Okuda H, Nakatani T, Sakamoto T, Yoshiji H, Fukui H, Ikenaka K, Mullen CA, Tsujii T (1999b) Cytosine deaminase/5-fluorocytosine gene therapy can induce efficient anti-tumor effects and protective immunity in immunocompetent mice but not in athymic nude mice. Int J Cancer 81: 592–597
    1. Melcher A, Todryk S, Hardwick N, Ford M, Jacobson M, Vile RG (1998) Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nature Med 4: 581–587
    1. Möller PH, Ivarsson K, Stenram U, Radnell M, Tranberg K-G (1997) Interstitial laser thermotherapy of an adenocarcinoma transplanted into rat liver. Eur J Surg 63: 867–870
    1. Möller PH, Ivarsson K, Stenram U, Radnell M, Tranberg K-G (1998) Comparison between interstitial laser thermotherapy and excision of an adenocarcinoma transplanted into rat liver. Br J Cancer 77: 1884–1892
    1. Möller PH, Lindberg L, Henriksson PH, Persson BRR, Tranberg K-G (1996) Temperature control and light penetration in a feedback interstitial laser thermotherapy system. Int J Hyperthermia 12: 49–63
    1. Morris JC (1999) Enzyme/prodrug-based tumor vaccination: all politics (and immunity) are local. J Natl Cancer Inst 91: 1986–1989
    1. Pierrefite-Carle V, Baque P, Gavelli A, Mala M, Chazal M, Gugenheim J, Bourgeon A, Milano G, Staccini P, Rossi B (1999) Cytosine deaminase/5-fluorocytosine-based vaccination against liver tumors: evidence of distant bystander effect. J Natl Cancer Inst 91: 2014–2019
    1. Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N (2000) 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
    1. Srivastava P (2002) Roles of heat-shock proteins in innate and adaptive immunity. Nat Rev Immunol 2: 185–194
    1. Steele GJ, Sjögren HO (1974) Cross-reacting tumor-associated antigen(s) among chemically induced rat colon carcinomas. Cancer Res 34: 1801–1807
    1. Sturesson C, Ivarsson K, Stenram U, Andersson-Engels S (2005) Interstitial laser-induced thermotherapy of a rat liver tumour: effect of temperature and hepatic inflow occlusion. Radiat Res (in press)
    1. Todryk S, Melcher AA, Hardwick N, Linardakis E, Bateman A, Colombo MP, Stoppacciaro A, Vile RG (1999) Heat shock protein 70 induced during tumor cell killing induces Th1 cytokines and targets immature dendritic cell precursors to enhance antigen uptake. J Immunol 163: 1398–1408
    1. Tranberg K-G, Möller PH, Hannesson P, Stenram U (1996) Interstitial laser treatment of malignant tumours: initial experience. Eur J Surg Oncol 22: 47–54
    1. Tranberg K-G, Myllymäki L, Möller PH, Ivarsson K, Sjögren HO (2002) Interstitial laser thermotherapy of a rat liver adenocarcinoma. J X-ray Sci Technol 10: 177–185
    1. Vogl TJ, Mack MG, Roggan A, Straub R, Eichler KC, Muller PK, Knappe V, Felix R (1998) Internally cooled power laser for MR-guided interstitial laser-induced thermotherapy of liver lesions: initial clinical results. Radiology 209: 381–385
    1. Wheatley DN, Kerr C, Gregory DW (1989) Heat-induced damage to HeLa-S3 cells: correlation of viability, permeability, osmosensitivity, phase-contrast light-, scanning electron-and transmission electron-microscopical findings. Int J Hyperthermia 5: 145–162
    1. Whiteland JL, Nicholls SM, Shimeld C, Easty DL, Williams NA, Hill TJ (1995) Immunohistochemical detection of T-cell subsets and other leukocytes in paraffin-embedded rat and mouse tissues with monoclonal antibodies. J Histochem Cytochem 43: 313–320
    1. Xiang R, Lode HN, Dreier T, Gillies SD, Reisfeld RA (1998) Induction of persistent tumor-protective immunity in mice cured of established colon carcinoma metastases. Cancer Res 58: 3918–3925
    1. Yamamoto S, Suzuki S, Hoshino A, Akimoto M, Shimada T (1997) Herpes simplex virus thymidine kinase/ganciclovir-mediated killing of tumor cell induces tumor-specific cytotoxic T cells in mice. Cancer Gene Ther 4: 91–96

Source: PubMed

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