Enhanced local and systemic anti-melanoma CD8+ T cell responses after memory T cell-based adoptive immunotherapy in mice
| Autor: | Prakrithi Srinand, M. Suresh, Siddhartha Sen, Andrew J. Tatar, Clifford S. Cho, Amanda Contreras, David A. Mahvi, Justin V. Meyers |
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| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Adoptive cell transfer Cell Survival T cell T-Lymphocytes Immunology Melanoma Experimental Biology CD8-Positive T-Lymphocytes Immunotherapy Adoptive Article 03 medical and health sciences Interleukin 21 Viral Proteins 0302 clinical medicine Cell Line Tumor medicine Immunology and Allergy Cytotoxic T cell Animals IL-2 receptor Antigen-presenting cell Antigens Viral Glycoproteins Natural killer T cell Flow Cytometry Peptide Fragments Tumor Burden Mice Inbred C57BL medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Female Memory T cell Immunologic Memory 030215 immunology |
| Zdroj: | Cancer immunology, immunotherapy : CII. 65(5) |
| ISSN: | 1432-0851 |
| Popis: | 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 naive, 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 demonstrate how the use of non-expanded memory CD8+ T cells may enhance ACT immunotherapeutic efficacy. |
| Databáze: | OpenAIRE |
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