CEA and NCA expressed by colon carcinoma cells affect their interaction with and lysability by activated lymphocytes.
Heterogeneous lysability by interleukin-2 activated lymphocytes (LAK) and other immune effectors was observed in the human colon-carcinoma lines LoVo/Dx, LoVo/H and HT29. The tumor cells with high susceptibility to LAK (LoVo/Dx, HT29) expressed higher amounts of the adhesion molecules ICAMl, LFA3 and NCA/CEA than cells with low LAK sensitivity (LoVo/H). Monoclonal antibodies against these molecules caused a marked reduction of lysis by LAK of LoVo/Dx and HT29. A pool of these antibodies induced a nearly complete inhibition of the LAK lysis of both lines. Treatment of LoVo/Dx with differentiating agents (dimethylformamide and retinoic acid) led to a decreased expression of the adhesion molecules, including NCA, accompanied by increased resistance to LAK-mediated lysis. Moreover, the presence of CEA soluble antigen drastically inhibited the cytotoxic activity of LAK effectors against HT29 and LoVo/Dx cells, in a dose-dependent manner. These data indicate that sensitivity of colon-carcinoma cells to activated lymphocytes depends on the level of expression of adhesion molecules, including CEA and NCA. Given the role of CEA-related antigens in tumor/lymphocyte interaction, soluble CEA, frequently released by colon-carcinoma, may be involved in immunosuppressive effects induced in vivo by tumor cells.
Rivoltini
L
L
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
Cattoretti
G
G
Arienti
F
F
Mastroianni
A
A
Parmiani
G
G
D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D002272:Carcinoembryonic Antigen / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D004126:Dimethylformamide / Q000494:pharmacology; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D014212:Tretinoin; D004126:Dimethylformamide