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. 1988 Apr;26(2):161–168. doi: 10.1007/BF00205610

Comparison of excision versus cryosurgery of an HSV-2-induced fibrosarcoma

I. Survival, extent of metastatic disease and host immunocompetence following surgery

Mark G Wing 1,✉, John R Goepel 2, George Jacob 3, Robert C Rees 4, Kenneth Rogers 1
PMCID: PMC11038626  PMID: 2834055

Abstract

Cryosurgery and excision were used to treat primary tumours of HSV-2-transformed hamster tumour sublines, and post-operative survival and the extent of meta-static disease were compared in the two groups. An inferior prognosis was observed following cryosurgery although the extent of metastatic disease was similar in both groups. Using this model it would appear that cryosurgery enhances the development of micrometastases rather than affecting the number of cells shed from the primary tumour during surgery. To investigate the underlying causes of the decrease in survival following cryosurgery, in vitro assays were used to monitor host immunocompetence following surgery. The results showed that whilst natural killer cell cytotoxicity was only marginally depressed, mitogen responsiveness and lymphocyte participation in a mixed lymphocyte reaction were severely reduced 3–7 days post-cryosurgery. In parallel with immunosuppression, extensive cell proliferation in the spleen of cryosurgically treated tumour-bearing animals was observed. Histological examination of the spleen demonstrated the presence of large numbers of transformed cells which correlated with the loss of mitogen responsiveness and the ability to participate in a mixed lymphocyte reaction. Further studies (manuscript submitted for publication) have demonstrated that spleen cells from animals whose tumour is treated by cryosurgery are capable of suppressing immunocompetence in vitro, implying they have a role in the uncontrolled growth of micrometastases in vivo.

Keywords: Primary Tumour, Natural Killer, Natural Killer Cell, Metastatic Disease, Spleen Cell

References

  • 1.Abraham E, Regan RF. The effect of hemorrhage and trauma on interleukin 2 production. Arch Surg. 1985;120:1341. doi: 10.1001/archsurg.1985.01390360007002. [DOI] [PubMed] [Google Scholar]
  • 2.Albin RJ, Soanes WA, Conder MJ. Prospects for cryo-immunotherapy in cases of metastasizing carcinoma of the prostate. Cryobiology. 1971;8:271. doi: 10.1016/0011-2240(71)90050-2. [DOI] [PubMed] [Google Scholar]
  • 3.Baker CC, Miller CL, Tranley DD, Lim RC. Identity of mononuclear cell which compromise the resistance of trauma patients. J Surg Res. 1979;26:478. doi: 10.1016/0022-4804(79)90037-4. [DOI] [PubMed] [Google Scholar]
  • 4.Bergman S, Borgstrom S, Tarnvik A. Lymphocyte response to phytohaemagglutinin following cholecystectomy. Acta Pathol Microb Scand. 1969;75:363. [PubMed] [Google Scholar]
  • 5.Bruce DL. Halothane inhibition of phytohaemagglutinin induced transformation of lymphocytes. Anesthesiology. 1972;36:201. doi: 10.1097/00000542-197203000-00001. [DOI] [PubMed] [Google Scholar]
  • 6.Crary B, Borysenke M, Sutherland DC. Decrease in mitogen responsiveness of mononuclear cells from peripheral blood after epinephrine administration in humans. J Immunol. 1983;130:694. [PubMed] [Google Scholar]
  • 7.Den Otter W. Immune surveillance and natural resistance: an evaluation. Cancer Immunol Immunother. 1986;21:85. doi: 10.1007/BF00199854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Faraci RP, Bagley DH, Marrone JC, Beazley RH. Effect of curative cryosurgery on the tumour-specific immune response of C57 mice. Cryobiology. 1975;12:175. doi: 10.1016/s0011-2240(75)80010-1. [DOI] [PubMed] [Google Scholar]
  • 9.Gillis S, Crabtree GR, Smith KA. Glucocorticoid-induced inhibition of T cell growth factor production. J Immunol. 1979;123:1624. [PubMed] [Google Scholar]
  • 10.Griffiths CDM, Rees RC, Platts A, Laurence AS, Rogers K. Enhanced natural killer cell activity in patients with malignant disease during intravenous anesthesia. J Clin Exp Cancer Res. 1983;2:399. [Google Scholar]
  • 11.Griffiths CDM, Rees RC, Platts A, Jermy A, Peel J, Rogers K. The nature of enhanced natural killer lymphocyte cytotoxicity during anesthesia and surgery in patients with benign disease and cancer. Ann Surg. 1984;200:753. doi: 10.1097/00000658-198412000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Grossman Z, Herberman RB. Immune Surveillance without immunogenicity. Immunol Today. 1986;7:128. doi: 10.1016/0167-5699(86)90075-7. [DOI] [PubMed] [Google Scholar]
  • 13.Gursel E, Roberts M, Veeneman RJ. Regression of prostatic cancer following sequential cryotherapy to the prostate. J Urol. 1972;108:928. doi: 10.1016/s0022-5347(17)60909-1. [DOI] [PubMed] [Google Scholar]
  • 14.Hellstrom I, Hellstrom KE, Sjogren HO, Warner GA. Serum factors in tumour-free patients cancelling the blocking of cell-mediated tumour immunity. Int J Cancer. 1971;8:185. doi: 10.1002/ijc.2910080202. [DOI] [PubMed] [Google Scholar]
  • 15.Herberman RB, Djen JY, Kay HD, Ortaldo JR, Riccardi C, Bonnard GD, Holden HT, Fagreni R, Santoni A, Rucetti P. Natural killer cells: characteristics and regulation of activity. Immunol Rev. 1979;44:48. doi: 10.1111/j.1600-065x.1979.tb00267.x. [DOI] [PubMed] [Google Scholar]
  • 16.Maier R, Holda JA, Claman HN. Natural suppressor cells — members of the LGL regulatory family. Immunol Today. 1986;7:312. doi: 10.1016/0167-5699(86)90069-1. [DOI] [PubMed] [Google Scholar]
  • 17.Miller CL, Baker CB. Changes in lymphocyte activity after thermal injury: the role of suppressor cells. J Clin Invest. 1979;63:202. doi: 10.1172/JCI109290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Minami A, Mizushima Y, Takeichi N, Hosokawa M, Kobayashi H. Dissociation of anti-tumour immune response in rats immunized with solubilized tumour-associated antigens from a methylcholanthrene-induced fibrosarcoma. Int J Cancer. 1979;23:358. doi: 10.1002/ijc.2910230314. [DOI] [PubMed] [Google Scholar]
  • 19.Neel HB, Ketcham AS, Hammond WG. Comparison of tumour immunity after complete excision, cryonecrosis and in the presence of persistent tumour. Surg Forum. 1973;21:120. [PubMed] [Google Scholar]
  • 20.Neel HB, Ketcham AS, Hammond WG. Experimental evaluation of in situ oncocide for primary tumour therapy: comparison of tumour specific immunity after complete excision, cryonecrosis and ligation. Laryngoscope. 1973;83:376. doi: 10.1288/00005537-197303000-00009. [DOI] [PubMed] [Google Scholar]
  • 21.Oehler JR. Modulation of immunity by macrophages. Pharmacol Ther. 1978;2:551. [Google Scholar]
  • 22.Prehn RT. The immune response as a stimulator of tumour growth. Science. 1972;176:170. doi: 10.1126/science.176.4031.170. [DOI] [PubMed] [Google Scholar]
  • 23.Pollock RE, Bubecock GF, Romsdahl MM, Nishioka K. Surgical stress-mediated suppression of murine natural killer cell cytotoxicity. Cancer Res. 1984;44:3888. [PubMed] [Google Scholar]
  • 24.Pollock RE, Lotzova E, Stanford SD, Romsdahl MN. Effect of surgical stress on murine natural killer cell cytotoxicity. J Immunol. 1987;138:171. [PubMed] [Google Scholar]
  • 25.Potter CW, Shortland JR, Mousaway KW, Rees RC. Comparative studies of transformed hamster cells by herpesvirus hominis types 1 and 2. Br J Exp Pathol. 1982;63:285. [PMC free article] [PubMed] [Google Scholar]
  • 26.Rand RW, Rinfret AP, Von Leden H. Cryosurgery. Springfield Ill: Chas C. Thomas; 1968. [Google Scholar]
  • 27.Schulman S, Yantorno C, Bronson P. Cryoimmunology — a method of immunisation to antologous tissue. Proc Soc Exp Biol Med. 1967;124:658. doi: 10.3181/00379727-124-31817. [DOI] [PubMed] [Google Scholar]
  • 28.Slade MS, Simmons RL, Yanis E, Greenberg LJ. Immunodepression after major surgery in normal patients. Surgery. 1975;78:363. [PubMed] [Google Scholar]
  • 29.Soanes WA, Albin RJ, Gonder MJ. Remission of metastatic lesions following cryosurgery in prostatic cancer: Immunological considerations. J Urol. 1970;104:154. doi: 10.1016/s0022-5347(17)61690-2. [DOI] [PubMed] [Google Scholar]
  • 30.Teale DM, Rees RC (1987) Hamster heterogenicity in a spontaneously metastatic HSV-2 induced fibrosarcoma. Association of phenotypic and genotypic properties with metastatic potential Invasion Metastasis I:129 [PubMed]
  • 31.Teale DM, Rees RC, Clarke A, Potter CW. Detection and characterisation of natural killer cells in Syrian golden hamsters. Eur J Cancer Clin Oncol. 1983;19:537. doi: 10.1016/0277-5379(83)90119-0. [DOI] [PubMed] [Google Scholar]
  • 32.Uchida A, Mickshe M. Lysis of fresh human tumour cells by autologous large granular lymphocytes from peripheral blood and effusions. Int J Cancer. 1983;32:37. doi: 10.1002/ijc.2910320107. [DOI] [PubMed] [Google Scholar]
  • 33.Walker JR, Rees RC, Teale DM, Potter CW. Properties of a herpes virus transformed hamster cell line. 1. Growth and culture characteristics of sublines of high and low metastatic potential. Eur J Cancer Clin Oncol. 1982;18:1017. doi: 10.1016/0277-5379(82)90251-6. [DOI] [PubMed] [Google Scholar]
  • 34.Wood JJ, Rodrich ML, O'Mahony JB, Palder SB, Saproschetz I, D'Eon P, Mannich JA. Inadequate interleukin-2 production — a fundamental immunological deficiency in patients with major burns. Ann Surg. 1984;200:311. doi: 10.1097/00000658-198409000-00008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Yamashita T, Hayakawa K, Hosokawa M, Kodama T, Inoue N, Tomita K, Kodayashi H. Enhanced tumour metastasis in rats following cryosurgery of primary tumour. Gann. 1982;73:222. [PubMed] [Google Scholar]

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