Abstract
Individual lymph nodes draining tumors vary in their degree of immunological activity. Cell suspensions from tumor-free nodes located relatively near to tumors are spontaneously less reactive and respond poorly to exogenous stimulation by mitogens and lymphokines. Diminished spontaneous uptake of tritiated thymidine by lymph node cells not exposed to exogenous stimulation suggests that tumor-proximate immune suppression exists in vivo and is not purely a laboratory artefact. The present study was undertaken to explore that possibility further. Fluid in which cell suspensions from tumor-free nodes were prepared, and supernatants from short-term cultures of nodes located at different distances from tumors were compared for their capacity to inhibit the in vitro migration of the human lymphoblastoid cell line QIMR-WIL. Inhibitory activity of fluids from individual nodes was related to their position relative to the tumor and their immune competence, assessed by the responses to mitogens of cell suspensions prepared from them. Cell suspension fluids from 92/111 nodes (83%) significantly inhibited the migration of QIMR-WIL, at a level similar (44±14%) to that induced by the supernatants of mixed lymphocyte cultures (43±17%). Fluids from the nodes of melanoma patients were more inhibitory than those from breast cancer patients (49±12% and 37±13%, respectively,P = 0.003). The inhibitory activity of the different nodes of individual node groups varied significantly in 25 of 33 patients (76%), the node nearest the tumor generating least inhibitory activity (indexing the greatest immune suppression) in 20 of these 25 patients (80%). The strength of migration-inhibitory activity was concordant with the responsiveness to mitogen stimulation in up to 14 of 18 patients (78%). Studies of molecular size and heat stability indicated that the inhibitory factors had characteristics consistent with common migration-inhibitory lymphokines such as leukocyte-migration-inhibitory factor, macrophage-inhibitory factor and interleukin-2. Our findings further support the hypothesis that lymph nodes nearest to tumors are relatively immune-suppressed in vivo.
Keywords: Immune Suppression, Lymph Node Cell, Lymphoblastoid Cell Line, Individual Lymph Node, Tritiated Thymidine
Footnotes
Supported by grants CA 29938 and CA 43658, awarded by the National Cancer Institute, DHHS and a grant from the Candle Foundation, Los Angeles
References
- 1.Cochran AJ, Wen D-R, Pihl EA, Fairhurst MV, Korn EL. tumor-proximate immune suppression of regional lymph nodes in patients with malignant melanoma. In: Hellman K, Eccles SA, editors. Treatment of metastases. London: Taylor and Francis; 1985. pp. 69–72. [Google Scholar]
- 2.Cochran AJ, Pihl EA, Wen D-R, Hoon DSB, Korn EL. Zoned imune suppression of lymph nodes draining malignant melanoma: histologic and immunohistologic studies. J Natl Cancer Inst. 1987;87:399–405. [PubMed] [Google Scholar]
- 3.Cochran AJ, Wen D-R, Morton DL. Occult melanoma cells in the lymph nodes of patients with pathological stage I malignant melanoma: an immunohistochemical study using antibodies to S-100 protein and the melanoma-directed monoclonal antibody NKI/C3. Am J Surg Pathol. 1988;12:612–618. doi: 10.1097/00000478-198808000-00002. [DOI] [PubMed] [Google Scholar]
- 4.Culbert EJ, Cochran AJ, Clements GB. Lymphoid cell lines as indicators of lymphokine generation. Scand J Immunol. 1982;16:163–169. doi: 10.1111/j.1365-3083.1982.tb00709.x. [DOI] [PubMed] [Google Scholar]
- 5.Culbert EJ, Cochran AJ, Wen D-R, Clements GB. The motility of the cells of a lymphoblastoid cell line, QIMRWIL, is inhibited by human and murine leukocyte inhibitory factor. In: Khan A, Hill NO, editors. Human lymphokines: biological immune modifiers. New York: Academic Press; 1982. pp. 41–55. [Google Scholar]
- 6.Hoon DSB, Wen D-R, Stene M, Gupta RK, Cochran AJ. Inhibition of lymphocyte motility by interleukin-2. Clin Exp Immunol. 1986;66:566–573. [PMC free article] [PubMed] [Google Scholar]
- 7.Hoon DSB, Korn EL, Cochran AJ. Variations in functional immune competence of individual tumor-draining lymph nodes in humans. Cancer Res. 1987;47:1740–1744. [PubMed] [Google Scholar]
- 8.Morrison LJ, Cochran AJ, Mackie RM, Ross CE, Todd G, Garland CG. A study of patients with malignant melanoma using an indirect leukocyte migration assay. Int J Cancer. 1979;24:1–16. doi: 10.1002/ijc.2910240104. [DOI] [PubMed] [Google Scholar]
- 9.Pope JH. Establishment of cell lines from Australian leukemic patients: presence of a herpes-like virus. Aust J Exp Biol Med Sci. 1968;46:643–648. doi: 10.1038/icb.1968.171. [DOI] [PubMed] [Google Scholar]
- 10.Rocklin RE, Remold HG, David JR. Characterization of human migratory inhibiting factor (MIF) from antigenstimulated lymphocytes. Cell Immunol. 1975;5:436–440. doi: 10.1016/0008-8749(72)90070-6. [DOI] [PubMed] [Google Scholar]