Adherent indomethacin-sensitive suppressor cells in malignant melanoma

Murray, J. G.; Springle, Claudette; Ishmael, D. Richard; Lee, Elisa T.; Longley, Ross E.; Kollmorgen, Gwendlyn; Nordquist, Robert L.

doi:10.1007/bf00199269

Cited by 10 publications

(4 citation statements)

References 32 publications

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“…[20]. Suppressor rnacrophages have been detected in the peripheral blood of melanoma patients [25], even in stages where no dysbalance in peripheral T cell subsets could be detected [19]. We have never found the 25F9 antigen on fresh peripheral blood monocytes from healthy volunteers.…”

Section: Discussionmentioning

confidence: 68%

Infiltration of primary and metastatic melanomas with macrophages of the 25F9-positive phenotype

Bröcker

Zwadlo

Suter

et al. 1987

Cancer Immunol Immunother

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In order to gain insight into the role of macrophages in human melanoma, we studied fresh-frozen material from 15 dysplastic nevi, 199 primary melanomas, 107 melanoma metastases, and paraffin sections from 98 primary melanomas with the monoclonal antibody 25F9 which recognizes an 86 x 10(3) dalton protein present on a subset of mature human macrophages. Considerable infiltration of tumors with 25F9-positive macrophages was observed in 2 dysplastic nevi (13%), 87 primary melanomas (44%), and 45 metastases (42%). The degree of intratumoral macrophage infiltration correlated with expression of class II HLA-DR antigens on tumor cells, in primary melanoma with a tumor thickness above 0.75 mm, and with the occurrence of metastases within 2 years. In paraffin sections, intratumoral 25F9-positive macrophages also correlated with metastatic spread of primary tumors after longer follow-up. Metastases revealed a higher degree of macrophage infiltration following systemic or local immunotherapy, compared with untreated metastases, or metastases removed during chemotherapy. Of 38 patients who died within an observation period of 1 year, 19 (50%) had considerable infiltration of metastases with 25F9-positive macrophages, whereas this was found in only 4 of 12 patients (33%), who survived for longer than 2 years following metastases removal. A higher degree of 25F9-positive macrophages correlated with a shift towards the T8-positive subsets within the T cell compartment of the infiltrate. Our results suggest that accumulation of 25F9-positive macrophages in melanomas indicates more aggressive tumor properties.

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Section: Discussionmentioning

confidence: 68%

Infiltration of primary and metastatic melanomas with macrophages of the 25F9-positive phenotype

Bröcker

Zwadlo

Suter

et al. 1987

Cancer Immunol Immunother

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“…This ef fect may partly be due to activation of suppressor Tcells expressing membrane receptors for PGE2 [20]. The fact that certain lymphocyte responses in vitro may be enhanced in the presence of cyclo-oxygenase inhibitors [4][5][6][7][8] further strengthens the role of PGs in immune regulation and suggests that lymphoid cells may produce and release these regulatory substances.…”

Section: Discussionmentioning

confidence: 98%

“…Members of both groups, which are known to interfere with lympho cyte responses, may be produced and released by monocytes [1][2][3]. Indirect support for the view that immunosuppressive effects of monocytes-macro phages are partly mediated by products of arachi donic acid comes from experiments showing aug mented mitogen responses in vitro in the presence of inhibitors of cyclo-oxygenase [4][5][6][7][8]. In contrast, it has been reported that inhibitors of lipoxygenase may re duce mitogen responses [9].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Enhancement of Mitogen Responses of Human Lymphocytes by Inhibitors of Cyclo-Oxygenase and 5,8,11-Eicosatriynoic Acid, an Inhibitor of 12-Lipoxygenase and Leukotriene Biosynthesis

Blomgren

Hammarström

Wasserman

1987

Int Arch Allergy Immunol

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Blood mononuclear cells are well-known producers of various cyclo-oxygenase and lipoxygenase metabolites of arachidonic acid, some of which possess immunoregulatory functions. In the present investigation, we have examined ³H-thymidine incorporation in human blood lymphocytes cultured with polyclonal mitogens and antigens in the presence of various inhibitors of cyclo-oxygenase (such as indomethacin and meclofenamic acid) and an inhibitor of 12-lipoxygenase and leukotriene biosynthesis, 5,8,11-eicosatriynoic acid (ETI). It was observed that these inhibitors could augment mitogen responses of nonpurified lymphocyte preparations but not of preparations which were depleted of monocytes. The results indicate that monocytes and not lymphocytes were the main producers of immunosuppressive eicosanoids derived from arachidonic acid. Further, mitogenic responses in the presence of both an inhibitor of cyclo-oxygenase and ETI were augmented to a higher extent than expected. Again, this enhancement was not observed in preparations depleted of monocytes. Arachidonic acid metabolism was examined in mitogen-stimulated cultures pulsed with ¹⁴C-arachidonic acid. It was observed that the production of three metabolites was inhibited by meclofenamic acid, whereas the amounts of another ¹⁴Cr-labeled compound were almost doubled in the presence of meclofenamic acid.

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“…Indomethacin-induced augmentation of lymphoproliferative responses (LPR) in peripheral blood mononuclear cells (PBMC) has been described in several types of human cancer [48], including Hodgkin's disease [19], gliomas [7], carcinomas of the head and neck [24,30,46], and melanomas [32,45]. The objectives of our study were to determine: (1) the frequency and degree of indomethacin-sensitive suppression in cultures of PBMC of head and neck cancer patients; (2) if the in vitro augmentation of LPR by indomethacin was related to synthesis of PGE; and (3) if the sensitivity of PBMC of the inhibitory action of PGE 2 was greater in individuals with elevated levels of indomethacin-sensitive suppression.…”

Section: Introductionmentioning

confidence: 99%

Indomethacin-induced augmentation of lymphoproliferative responses in patients with head and neck cancer

McCormick

Panje

1986

Cancer Immunol Immunother

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Augmentation of the phytohemagglutinin (PHA)-induced lymphoproliferation of peripheral blood mononuclear cells by indomethacin, a drug which blocks prostaglandin (PG) synthesis, was assessed in 37 patients with squamous cell carcinoma of the head and neck. Indomethacin enhanced the uptake of 3H-thymidine in stimulated cultures both from patients and normal individuals. However, because lymphoid cells from cancer patients were less reactive than those from normal controls, the proportionate increase in PHA-stimulated 3H-thymidine incorporation caused by indomethacin was greater in this population than in the normal population. The degree of enhancement induced by indomethacin did not correlate with the percent of esterase-positive mononuclear cells in the preparations. The amounts of PGE synthesized at 48 h by patients' or normal cells were similar. Cell populations that exhibited elevated levels of augmentation in the presence of indomethacin were approximately 3 times as sensitive to inhibition by 3 nM PGE2. The degree of augmentation detected in the presence of Ro-20-5720, which also prevents PG synthesis, was related to that produced by indomethacin. These results suggested that: the enhancing effect of indomethacin on lymphoproliferation in vitro was related to its inhibition of PG synthesis; and the sensitivity of lymphoid cells to inhibition by PGE2 was slightly, but significantly, increased in individuals with elevated augmentation values.

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Adherent indomethacin-sensitive suppressor cells in malignant melanoma

Cited by 10 publications

References 32 publications

Infiltration of primary and metastatic melanomas with macrophages of the 25F9-positive phenotype

Infiltration of primary and metastatic melanomas with macrophages of the 25F9-positive phenotype

Synergistic Enhancement of Mitogen Responses of Human Lymphocytes by Inhibitors of Cyclo-Oxygenase and 5,8,11-Eicosatriynoic Acid, an Inhibitor of 12-Lipoxygenase and Leukotriene Biosynthesis

Indomethacin-induced augmentation of lymphoproliferative responses in patients with head and neck cancer

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