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T-cell subsets in peripheral blood and tumors of patients treated with oncolytic adenoviruses.

ABSTRACT: 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.

SUBMITTER: Taipale K 

PROVIDER: S-EPMC4427873 | biostudies-other | 2015 May

REPOSITORIES: biostudies-other

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T-cell subsets in peripheral blood and tumors of patients treated with oncolytic adenoviruses.

Taipale Kristian K   Liikanen Ilkka I   Juhila Juuso J   Karioja-Kallio Aila A   Oksanen Minna M   Turkki Riku R   Linder Nina N   Lundin Johan J   Ristimäki Ari A   Kanerva Anna A   Koski Anniina A   Joensuu Timo T   Vähä-Koskela Markus M   Hemminki Akseli A  

Molecular therapy : the journal of the American Society of Gene Therapy 20150206 5

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-  ...[more]