Τίτλος:
Antitumor reactive T-cell responses are enhanced in vivo by DAMP prothymosin alpha and its C-terminal decapeptide
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Prothymosin α (proTα) and its C-terminal decapeptide proTα(100–109) were shown to pleiotropically enhance innate and adaptive immune responses. Their activities have been broadly studied in vitro, focusing primarily on the restoration of the deficient immunoreactivity of cancer patients’ leukocytes. Previously, we showed that proTα and proTα(100–109) act as danger-associated molecular patterns (DAMPs), ligate Toll-like receptor-4, signal through TRIF-and MyD88-dependent pathways, promote the maturation of dendritic cells and elicit T-helper type 1 (Th1) immune responses in vitro, leading to the optimal priming of tumor antigen-reactive T-cell functions. Herein, we assessed their activity in a preclinical melanoma model. Immunocompetent mice bearing B16.F1 tumors were treated with two cycles of proTα or proTα(100–109) together with a B16.F1-derived peptide vaccine. Coadministration of proTα or proTα(100–109) and the peptide vaccine suppressed melanoma-cell proliferation, as evidenced by reduced tumor-growth rates. Higher melanoma infiltration by CD3+ T cells was observed, whereas ex vivo analysis of mouse total spleen cells verified the in vivo induction of melanoma-reactive cytotoxic responses. Additionally, increased levels of proinflammatory and Th1-type cytokines were detected in mouse serum. We propose that, in the presence of tumor antigens, DAMPs proTα and proTα(100–109) induce Th1-biased immune responses in vivo. Their adjuvant ability to orchestrate antitumor immunoreactivities can eventually be exploited therapeutically in humans. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Birmpilis, A.I.
Karachaliou, C.-E.
Samara, P.
Ioannou, K.
Selemenakis, P.
Kostopoulos, I.V.
Kavrochorianou, N.
Kalbacher, H.
Livaniou, E.
Haralambous, S.
Kotsinas, A.
Farzaneh, F.
Trougakos, I.P.
Voelter, W.
Dimopoulos, M.-A.
Bamias, A.
Tsitsilonis, O.
Λέξεις-κλειδιά:
antineoplastic agent; gamma interferon; interleukin 10; interleukin 17; interleukin 2; interleukin 4; interleukin 6; peptide vaccine; prothymosin alpha; threonyllysyllysylglutamyllysylthreonylaspartylglutamylaspartylaspartic acid; tumor antigen; tumor necrosis factor; unclassified drug, animal cell; animal experiment; animal model; animal tissue; antineoplastic activity; antiproliferative activity; Article; cancer inhibition; carboxy terminal sequence; CD3+ T lymphocyte; cell mediated cytotoxicity; controlled study; cytokine production; ex vivo study; immunoreactivity; in vivo study; lymphocytic infiltration; male; melanoma; melanoma cell; mouse; multiple cycle treatment; natural killer cell; nonhuman; Th1 cell
DOI:
10.3390/cancers11111764
