title: Soluble OX40L favors tumor rejection in CT26 colon carcinoma model.
abstract: OX40 receptor-expressing regulatory T cells (Tregs) populate tumors and suppress a variety of immune cells, posing a major obstacle for cancer immunotherapy. Different ways to functionally inactivate Tregs by triggering OX40 receptor have been suggested, including anti-OX40 antibodies and Fc:OX40L fusion proteins. To investigate whether the soluble extracellular domain of OX40L (OX40Lexo) is sufficient to enhance antitumor immune response, we generated an OX40Lexo-expressing CT26 colon carcinoma cell line and studied its tumorigenicity in immunocompetent BALB/c and T cell deficient nu/nu mice. We found that soluble OX40L expressed in CT26 colon carcinoma favors the induction of an antitumor response which is not limited just to cells co-expressing EGFP as an antigenic determinant, but also eliminates CT26 cells expressing another fluorescent protein, KillerRed. Tumor rejection required the presence of T lymphocytes, as indicated by the unhampered tumor growth in nu/nu mice. Subsequent re-challenge of tumor-free BALB/c mice with CT26 EGFP cells resulted in no tumor growth, which is indicative of the formation of immunological memory. Adoptive transfer of splenocytes from mice that successfully rejected CT26 OX40Lexo EGFP tumors to naïve mice conferred 100% resistance to subsequent challenge with the CT26 EGFP tumor.
authors.affiliation: Nizhny Novgorod State Medical Academy, 603005 Minin and Pozharsky Sq., 10/1, Nizhny Novgorod, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997, Miklukho-Maklaya St., 16/10, Moscow, Russia. Electronic address: katya_akts@mail.ru.
authors.forename: Ekaterina O
authors.initials: EO
authors.lastname: Serebrovskaya
authors.affiliation: Nizhny Novgorod State Medical Academy, 603005 Minin and Pozharsky Sq., 10/1, Nizhny Novgorod, Russia; Lobachevsky State University of Nizhny Novgorod, 603950 Gagarina Ave., 23, Nizhny Novgorod, Russia.
authors.forename: Diana V
authors.initials: DV
authors.lastname: Yuzhakova
authors.affiliation: Nizhny Novgorod State Medical Academy, 603005 Minin and Pozharsky Sq., 10/1, Nizhny Novgorod, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997, Miklukho-Maklaya St., 16/10, Moscow, Russia.
authors.forename: Alina P
authors.initials: AP
authors.lastname: Ryumina
authors.affiliation: Nizhny Novgorod State Medical Academy, 603005 Minin and Pozharsky Sq., 10/1, Nizhny Novgorod, Russia.
authors.forename: Irina N
authors.initials: IN
authors.lastname: Druzhkova
authors.affiliation: Moscow State University, Faculty of Medicine, 119192, Lomonosovsky pr., 31/5, Moscow, Russia.
authors.forename: George V
authors.initials: GV
authors.lastname: Sharonov
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997, Miklukho-Maklaya St., 16/10, Moscow, Russia.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Kotlobay
authors.affiliation: Nizhny Novgorod State Medical Academy, 603005 Minin and Pozharsky Sq., 10/1, Nizhny Novgorod, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Zagaynova
authors.affiliation: Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997, Miklukho-Maklaya St., 16/10, Moscow, Russia; Pirogov Russian National Research Medical University, 117997, Ostrovityanova st., 1, Moscow, Russia.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Lukyanov
authors.affiliation: Nizhny Novgorod State Medical Academy, 603005 Minin and Pozharsky Sq., 10/1, Nizhny Novgorod, Russia.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Shirmanova
mesh_terms: D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D002277:Carcinoma / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D005260:Female; D049452:Green Fluorescent Proteins / Q000276:immunology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology / Q000502:physiology; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053278:OX40 Ligand / Q000276:immunology / Q000378:metabolism*; D053262:Receptors, OX40 / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D053278:OX40 Ligand; D053262:Receptors, OX40; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: Antitumor immune response; CT26 colon carcinoma; Immunological memory; Soluble OX40L; Tumorigenicity