T-cell Subsets in Peripheral Blood and Tumors of Patients Treated With Oncolytic Adenoviruses

• Published in: Molecular therapy Vol. 23; no. 5; pp. 964 - 973
• Main Authors: Kristian, Taipale, Ilkka, Liikanen, Juuso, Juhila, Aila, Karioja-Kallio, Minna, Oksanen, Riku, Turkki, Nina, Linder, Johan, Lundin, Ari, Ristimäki, Anna, Kanerva, Anniina, Koski, Timo, Joensuu, Markus, Vähä-Koskela, Akseli, Hemminki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2015; Elsevier Limited; Nature Publishing Group
• Subjects: Adenoviridae; Adenoviridae - genetics; Adenovirus; Adenoviruses; Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; Bone cancer; Cancer therapies; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cells; Child; Cytotoxicity; Female; Gene therapy; Genetic Therapy; Humans; Immune system; Immunotherapy; Lymphocyte Count; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Male; Middle Aged; Neoplasms - diagnosis; Neoplasms - genetics; Neoplasms - immunology; Neoplasms - therapy; Oncolytic Virotherapy; Oncolytic Viruses - genetics; Original; Pathology; Patients; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Tomography; Transduction, Genetic; Transgenes; Tumors; Viruses; Young Adult; Finland
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1038/mt.2015.17

The quality of the antitumor immune response is decisive when developing new immunotherapies for cancer. Oncolytic adenoviruses cause a potent immunogenic stimulus and arming them with costimulatory molecules reshapes the immune response further. We evaluated peripheral blood T-cell subsets of 50 patients with refractory solid tumors undergoing treatment with oncolytic adenovirus. These data were compared to changes in antiviral and antitumor T cells, treatment efficacy, overall survival, and T-cell subsets in pre- and post-treatment tumor biopsies. Treatment caused a significant (P < 0.0001) shift in T-cell subsets in blood, characterized by a proportional increase of CD8+ cells, and decrease of CD4+ cells. Concomitant treatment with cyclophosphamide and temozolomide resulted in less CD4+ decrease (P = 0.041) than cyclophosphamide only. Interestingly, we saw a correlation between T-cell changes in peripheral blood and the tumor site. This correlation was positive for CD8+ and inverse for CD4+ cells. These findings give insight to the interconnections between peripheral blood and tumor-infiltrating lymphocyte (TIL) populations regarding oncolytic virotherapy. In particular, our data suggest that induction of T-cell response is not sufficient for clinical response in the context of immunosuppressive tumors, and that peripheral blood T cells have a complicated and potentially misleading relationship with TILs.