Summary
To elucidate the mechanism of action for intratumoral injection of immunopotentiators, infiltrating mononuclear cells and tumor necrosis factor (TNF) were assayed by immunostaining tissue samples of differentiated thyroid cancer resected with or without presurgical local application of OK-432, a streptococcal preparation. Frozen sections of resected specimens were stained with monoclonal antibodies using either a conventional or a modified immunoperoxidase method. The tumors injected with OK-432 showed increased T lymphocyte infiltration and HLA-DR expression on cancer cells as compared to the non-injected controls. Among these T cells, the CD4+ subset was more numerous than the CD8+ population. In four out of the seven cases constituting the injected group, numerous TNF-positive cells were seen in clusters or lines as well as scattered, while none of the seven cases in the control group was associated with a considerable amount of these cells. In their morphology and distribution pattern, these TNF-positive cells appeared to be of macrophage lineage. Thus local injection of OK-432 in thyroid cancer was shown to recruit T lymphocytes of predominantly the CD4+ subset and to induce in situ production of TNF, a known potent tumoricidal cytokine. The present data warrant further studies in this direction besides wider clinical intratumoral application of the reagent.
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References
Aggarwal BB, Kohr WJ, Hass PE, Moffat B, Spencer SA, Henzel WJ, Bringman TS, Nedwin GE, Goeddel DV, Harkins RN (1985) Human tumor necrosis factor. J Biol Chem 260: 2345
Akura Y, Tanaka N, Kobayashi G, Gotoh A, Gouchi A, Kamitani S, Gangi J, Orita K (1986) The effects of intratumoral OK-432 injection in gastric cancer patients. In: Tobe T (ed), New applications of OK-432. Excerpta Medica, Tokyo, p 75
Chensue SW, Remick DG, Shmyr-Forsch C, Beals TF, Kunkel S (1988) Immunohistochemical demonstration of cytoplasmic and membrane-associated tumor necrosis factor in murine macrophages. Am J Pathol 133: 564
Hojo H, Hashimoto Y (1981) Cytotoxic cells induced in tumor-bearing rats by a streptococcus preparation (OK-432). Gann 72: 692
Ichimura O, Suzuki S, Saito M, Sugawara Y, Ishida N (1985) Augmentation of interleukin 1 and interleukin 2 production by OK-432. Int J Immunopharmacol 7: 263
Kokunai I, Shimano T, Sekimoto K, Takeda T, Kobayashi T, Yayoi E, Yamamoto A, Mori T (1986) Induction of tumor necrosis factor by administration of OK-432 in cancer patients. J Clin Lab Immunol 21: 169
Kraiem Z, Sobel E, Sadeh O, Kinarty S, Lahat N (1990) Effects of γ-interferon on DR antigen expression, growth, 3,5,3′-triiodothyronine secretion, iodide uptake, and cyclic adenosine 3′,5′-monophosphate accumulation in cultured human thyroid cells. J Clin Endocrinol Metab 71: 817
Misaki T, Dokoh S (1990) Two cases of differentiated thyroid cancer treated with local injection of OK-432 (in Japanese). Ther Res 11: 3779
Misaki T, Konishi J, Nakashima T, Iida Y, Kasagi K, Endo K, Uchiyama T, Kuma K, Torizuka K (1985) Immunohistological phenotyping of thyroid infiltrating lymphocytes in Graves' disease and Hashimoto's thyroiditis. Clin Exp Immunol 60: 104
Misaki T, Tramontano D, Ingbar SH (1988) Effects of rat γ- and non-γ-interferons on the expression of Ia antigen, growth, and differentiated functions of FRTL5 cells. Endocrinology 123: 2849
Miwa H, Gohchi A, Moriyasu F, Orita K (1984) Increase in T cell infiltration in carcinoma tissue and regional lymph node reaction to gastric cancer after local injection of immunomodulators before gastrectomy. In: Aoki T, Tsubura E, Urushizaki I (eds) Manipulation of host defence mechanisms. Excerpta Medica, Amsterdam, p 13
Oettgen HF, Old LJ (1987) Tumor necrosis factor. In: Rosenberg SA, Herrman S, DeVita VT Jr (eds) Important advances in oncology. Lippincott, Philadelphia, p 105
Saito M, Ebina T, Koi M, Yamaguchi T, Kawade Y, Ishida N (1982) Induction of interferon-γ in mouse spleen cells by OK-432, a preparation ofStreptococcus pyogenes. Cell Immunol 68: 187
Saito M, Nanjo M, Aonuma E, Noda T, Nakadate I, Ebina T, Ishida N (1984) Activated macrophages are responsible for the tumor-inhibitory effect in mice receiving intravenous injection of OK-432. Int J Cancer 33: 271
Sawaki S, Tsukuda M, Mitarai K (1986) Clinical evaluation of nonspecific immunotherapy with OK-432 for head and neck cancer. In: Ota K (ed) Clinical application of OK-432 for control of cancer. Excerpta Medica, Tokyo, p 255
Selby P, Hobbs S, Viner C, Jackson E, Jones A, Newell D, Calvert AH, McElwain T, Fearon K, Humphreys J, Shiga T (1987) Tumour necrosis factor in man: clinical and biological observations. Br J Cancer 56: 803
Stötter H, Wiebke EA, Tomita S, Belldegrun A, Topalian S, Rosenberg SA, Lotze MT (1989) Cytokines alter target cell susceptability to lysis. II. Evaluation of tumor infiltrating lymphocytes. J Immunol 142: 1767
Sugenoya A, Usuda N, Adachi W, Kaneko G, Nagata T, Iida F (1988) Immunohistochemical studies on local antitumor effects of streptococcal immunopotentiator, OK-432, in human solid malignant tumors. Arch Pathol Lab Med 112: 545
Umesaki N, Ooshita Y, Kawabata M, Sako H, Sugawa T (1986) Experimental and clinical efficacy of locally administered OK-432, in particular against gynecological cancer. In: Tobe T (ed) New applications of OK-432. Excerpta Medica, Tokyo, p 102
Urban JL, Rothstein JL, Shephard MH, Schreiber H (1987) Tumornecrosis factor: a potent mediator of macrophage-dependant tumorcell killing. Haematol Blood Trans 31: 351
Watanabe N, Niitsu Y, Yamauchi N, Neda H, Sone H, Urushizaki I, Yamamoto A, Nagamuta M, Sugawara Y (1988) Therapeutic effect of OK-432 induced endogenous TNF on tumor bearing mice and cancer patients. Immunopharmacol Immunotoxicol 10: 53
Watanabe Y, Yamada T, Hashizume Y, Iwa T (1986) Clinical value of immunotherapy with the streptococcal preparation, OK-432 for lung cancer: a randomized study. In: Ota K (ed) Clinical application of OK-432 for control of cancer. Excerpta Medica, Tokyo, p 105
Yagita A, Watanabe Y, Ito H, Tatekawa I, Saito M, Ishida N (1986) Relationship between HLA antigens and immune response in Su-PS skin tests, and between the H-2 system and blastogenic activity in the presence of OK-432. In: Hoshino T (ed) Immunopharmacological aspects of OK-432 in humans. Excerpta Medica, Tokyo, p 225
Yamamoto A, Nagamuta M, Usami H, Sugawara Y, Watanabe N, Niitsu Y, Urushizaki I (1986) Release of tumor necrosis factor (TNF) into mouse peritoneal fluids by OK-432, a streptococcal preparation. Immunopharmacology 11: 79
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Misaki, T., Watanabe, Y., Iida, Y. et al. Recruitment of T lymphocytes and induction of tumor necrosis factor in thyroid cancer by a local immunotherapy. Cancer Immunol Immunother 35, 92–96 (1992). https://doi.org/10.1007/BF01741855
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DOI: https://doi.org/10.1007/BF01741855