Lymphotactin expression by engineered myeloma cells drives tumor regression: mediation by CD4+ and CD8+ T cells and neutrophils expressing XCR1 receptor.
The C chemokine lymphotactin has been characterized as a T cell chemoattractant both in vitro and in vivo. To determine whether lymphotactin expression within tumors could influence tumor growth, we transfected an expression vector for lymphotactin into SP2/0 myeloma cells and tested their ability to form tumors in BALB/c and nude mice. Transfection did not alter cell growth in vitro. Whereas SP2/0 cells gave rise to a 100% tumor incidence, lymphotactin-expressing SP2/0-Lptn tumors invariably regressed in BALB/c mice and became infiltrated with CD4(+) and CD8(+) T cells and neutrophils. Regression of the SP2/0-Lptn tumors was associated with a type 1 cytokine response and dependent on both CD4(+) and CD8(+) T cells, but not NK cells. Both SP2/0 and SP2/0-Lptn tumors grew in nude mice, but growth of the latter tumors was retarded and associated with heavy neutrophil responses; this retardation of SP2/0-Lptn tumor growth was reversed by neutrophil depletion of the mice. Our data also indicate that mouse neutrophils express the lymphotactin receptor XCR1 and that lymphotactin specifically chemoattracts these cells in vitro. Thus, lymphotactin has natural adjuvant activities that may augment antitumor responses via effects on both T cells and neutrophils and thereby could be important in gene transfer immunotherapies for some cancers.
Cairns
C M
CM
Department of Microbiology, Saskatoon Cancer Center, Saskatoon, Saskatchewan, Canada.
Gordon
J R
JR
Li
F
F
Baca-Estrada
M E
ME
Moyana
T
T
Xiang
J
J
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use; D019744:Chemokines, C / Q000235:genetics / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D007279:Injections, Subcutaneous; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009101:Multiple Myeloma / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D009368:Neoplasm Transplantation; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D015202:Protein Engineering; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D043562:Receptors, G-Protein-Coupled; D012795:Sialoglycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation
D019496:Cancer Vaccines; D019744:Chemokines, C; D008222:Lymphokines; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012795:Sialoglycoproteins; C092390:XCL1 protein, human; C091671:XCR1 protein, human; C486249:Xcl1 protein, mouse; C018997:lymphotactin