Improvement of Antitumor Therapies Based on Vaccines and Immune-Checkpoint Inhibitors by Counteracting Tumor-Immunostimulation
| العنوان: | Improvement of Antitumor Therapies Based on Vaccines and Immune-Checkpoint Inhibitors by Counteracting Tumor-Immunostimulation |
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| المؤلفون: | Richmond T. Prehn, Mónica Vermeulen, Ariel Ramiro Strazza, Pablo Vallecorsa, Daniela Romina Montagna, Roberto Meiss, Paula Chiarella, Oscar D. Bustuoabad, Raúl A. Ruggiero |
| المصدر: | Frontiers in Oncology Frontiers in Oncology, Vol 8 (2018) CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET |
| بيانات النشر: | Frontiers Media SA, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Chemokine, CIENCIAS MÉDICAS Y DE LA SALUD, Immune checkpoint inhibitors, p38 mitogen-activated protein kinases, Inmunología, immunosurveillance, Stimulation, lcsh:RC254-282, murine tumors, 03 medical and health sciences, 0302 clinical medicine, Immune system, MURINE TUMORS, IMMUNE-CHECKPOINTS INHIBITORS, tumor-immunostimulation, Receptor, Original Research, biology, Chemistry, IMMUNOSURVEILLANCE, ANTITUMOR VACCINES, purl.org/becyt/ford/3.1 [https], lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, TUMOR-IMMUNOSTIMULATION, immune-checkpoints inhibitors, Immunosurveillance, Medicina Básica, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, biology.protein, purl.org/becyt/ford/3 [https], antitumor vaccines, Signal transduction |
| الوصف: | Immune-checkpoint inhibitors and antitumor vaccines may produce both tumor-inhibitory and tumor-stimulatory effects on growing tumors depending on the stage of tumor growth at which treatment is initiated. These paradoxical results are not necessarily incompatible with current tumor immunology but they might better be explained assuming the involvement of the phenomenon of tumor immunostimulation. This phenomenon was originally postulated on the basis that the immune response (IR) evoked in Winn tests by strong chemical murine tumors was not linear but biphasic, with strong IR producing inhibition and weak IR inducing stimulation of tumor growth. Herein, we extended those former observations to weak spontaneous murine tumors growing in pre-immunized, immune-competent and immune-depressed mice. Furthermore, we demonstrated that the interaction of specifical T cells and target tumor cells at low stimulatory ratios enhanced the production of chemokines aimed to recruit macrophages at the tumor site, which, upon activation of toll-like receptor 4 and p38 signaling pathways, would recruit and activate more macrophages and other inflammatory cells which would produce growth-stimulating signals leading to an accelerated tumor growth. On this basis, the paradoxical effects achieved by immunological therapies on growing tumors could be explained depending upon where the therapy-induced IR stands on the biphasic IR curve at each stage of tumor growth. At stages where tumor growth was enhanced (medium and large-sized tumors), counteraction of the tumor-immunostimulatory effect with anti-inflammatory strategies or, more efficiently, with selective inhibitors of p38 signaling pathways enabled the otherwise tumor-promoting immunological strategies to produce significant inhibition of tumor growth. Fil: Chiarella, Paula. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Vermeulen, Mónica. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Montagna, Daniela R.. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Vallecorsa, Pablo. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Strazza, Ariel Ramiro. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Bustuoabad, Oscar D.. Retired; Argentina Fil: Ruggiero, Raúl A.. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Prehn, Richmond T.. University Of Washington, Seattle |
| وصف الملف: | application/pdf |
| تدمد: | 2234-943X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6e85a6822b513358350d56952af7f4d https://doi.org/10.3389/fonc.2018.00006 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d6e85a6822b513358350d56952af7f4d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2234943X |
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