Enhanced local and systemic anti-melanoma CD8+ T cell responses after memory T cell-based adoptive immunotherapy in mice

Abstract Adoptive cell transfer (ACT) melanoma immunotherapy typically employs acutely activated effector CD8+ T cells for their ability to rapidly recognize and clear antigen. We have previously observed that effector CD8+ T cells are highly susceptible to melanoma-induced suppression, whereas memory CD8+ T cells are not. Although memory T cells have been presumed to be potentially advantageous for ACT, the kinetics of local and systemic T cell responses after effector and memory ACT have not been compared. B16F10 melanoma cells stably transfected to express very low levels of the lymphocytic choriomeningitis virus (LCMV) peptide GP33 (B16GP33) were inoculated into syngeneic C57BL/6 mice. Equal numbers of bona fide naïve, effector, or memory phenotype GP33-specific CD8+ T cells were adoptively transferred into mice 1 day after B16GP33 inoculation. The efficacy of ACT immunotherapy was kinetically assessed using serial tumor measurements and flow cytometric analyses of local and systemic CD8+ T cell responses. Control of B16GP33 tumor growth, persistence of adoptively transferred CD8+ cells, intratumoral infiltration of CD8+ T cells, and systemic CD8+ T cell responsiveness to GP33 were strongest after ACT of memory CD8+ T cells. Following surgical tumor resection and melanoma tumor challenge, only mice receiving memory T cell-based ACT immunotherapy exhibited durable tumor-specific immunity. These findings demons...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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We describe a case series of nine patients with metastatic melanoma and injectable lesions who developed progressive disease under a PD-1 inhibitor monotherapy. At the time of progressive disease, patients received intratumoral IL-2 treatment in addition to PD-1 inhibitor therapy. Three patients showed complete, three patients partial response and three patients progressive disease upon this combination therapy. IHC stainings were performed from metastases available at baseline (start of PD-1 inhibitor) and under combination therapy with IL-2. IHC results revealed a significant increase of CD4+ and CD8+ T cells and a highe...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
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Source: Asbestos and Mesothelioma News - Category: Environmental Health Authors: Source Type: news
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Source: Annual Review of Medicine - Category: General Medicine Authors: Tags: Annu Rev Med Source Type: research
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Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
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Source: EyeForPharma - Category: Pharmaceuticals Authors: Source Type: news
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Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
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Source: Applied Microbiology and Biotechnology - Category: Microbiology Authors: Tags: Appl Microbiol Biotechnol Source Type: research
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Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
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Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
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Source: Journal of Immunotherapy - Category: Allergy & Immunology Tags: Basic Studies Source Type: research
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