Blog
About

0
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found
      Is Open Access

      Recurrence of melanoma following T cell treatment: continued antigen expression in a tumor that evades T cell recruitment.

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Clinical therapy with T cells shows promise for cancer patients, but is currently challenged by incomplete responses and tumor relapse. The exact mechanisms that contribute to tumor relapse remain largely unclear. Here, we treated mouse melanomas with T cell receptor-engineered T cells directed against a human peptide-major histocompatibility complex antigen in immune-competent mice. T cells resulted in significant tumor regression, which was followed by relapse in about 80-90% of mice. Molecular analysis revealed that relapsed tumors harbored nonmutated antigen genes, not silenced by promoter methylation, and functionally expressed surface antigen at levels equal to nontreated tumors. Relapsed tumors resisted a second in vivo T cell treatment, but regained sensitivity to T cell treatment upon retransplantation in mice. Notably, relapsed tumors demonstrated decreased levels of CD8 T cells and monocytes, which were substantiated by downregulated expression of chemoattractants and adhesion molecules. These observations were confirmed when using T cells specific for a less immunogenic, endogenous mouse melanoma antigen. We conclude that tumors, when exposed to T cell treatment, can relapse without loss of antigen and develop a milieu that evades recruitment of effector CD8 T cells. Our findings support the concept to target the tumor milieu to aid T cell therapy in limiting tumor relapse.

          Related collections

          Author and article information

          Affiliations
          [1 ] Laboratory of Tumor Immunology, Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
          [2 ] Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Cardiff, UK.
          [3 ] Institute de Génétique Moléculaire de Montpellier, Université Montpellier, Montpellier, France.
          [4 ] Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
          Journal
          Mol. Ther.
          Molecular therapy : the journal of the American Society of Gene Therapy
          1525-0024
          1525-0016
          Feb 2015
          : 23
          : 2
          mt2014215 10.1038/mt.2014.215 25363716 4445618

          Comments

          Comment on this article