Cargo from tumor-expressed albumin inhibits T-cell activation and responses.
In this study, we show that rodent albumin is expressed by and cell surface localized on at least some murine tumor cells. We have been able to purify this tumor-expressed albumin from in vivo grown tumor masses. The tumor-expressed albumin, unlike normal serum albumin purified from blood, is capable of inhibiting T-cell activation, proliferation, and function in both in vitro and in vivo settings. Tumor-expressed albumin does not appear to affect antigen processing or presentation by professional antigen-presenting cells. The activity appears to lie in relatively small, lipid-like moieties that are presumably cargo for tumor-expressed albumin, and that activity can be removed from the albumin by lipid removal or treatment with lipase. Thus, we herein report of a novel form of tumor-induced immune suppression attributable to lipid-like entities, cloaked by albumin produced by tumors.
Graner
Michael W
MW
Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona, Arizona Health Sciences Center, Tucson, Arizona, USA. michael.graner@duke.edu
Likhacheva
Anna
A
Davis
Jane
J
Raymond
Amy
A
Brandenberger
Jared
J
Romanoski
Angela
A
Thompson
Sylvia
S
Akporiaye
Emmanuel
E
Katsanis
Emmanuel
E
D000418:Albumins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008055:Lipids / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology
D000418:Albumins; D007166:Immunosuppressive Agents; D008055:Lipids; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta