T cell assays and MIATA: the essential minimum for maximum impact.

The Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA*Correspondence: cedrik.britten@tron-mainz.dehttp://dx.doi.org/10.1016/j.immuni.2012.07.010The field of immunology has recentlyexperienced enormous advances fromwhich most have so far not been incorpo-rated into standard medical practice (Da-vis, 2008). One approach to fully exploitthe existing wealth of knowledge is toimplement a systematic strategy to eval-uate the immune system. The potentialbenefit of such an approach is that itmay lead to results that can be translatedinto the rational development of diagnos-tics and therapeutics (Hoos et al., 2011).Two prerequisites for its application ar…

The role of the reporting framework MIATA within current efforts to advance immune monitoring

Flow Cytometry in Cancer Immunotherapy: Applications, Quality Assurance, and Future

Cancer immunotherapy seeks to elicit or augment the antitumor immune response in a patient in order to enlist the help of the patient’s own immune system for tumor control. In this context, immune monitoring provides evidence of immunogenicity, guides the choice and dosage of antigens, assesses the effects of immune modulators and therapy combinations, and has the potential to reveal early biomarkers of clinical efficacy. In view of their role in the anticancer immune response, the quantity and quality of tumor antigen-specific effector CD4+ and CD8+ T cells are of particular interest, and characterization of regulatory T cells and myeloid-derived suppressor cells is increasingly relevant. …

Cryopreservation of MHC Multimers: Recommendations for Quality Assurance in Detection of Antigen Specific T Cells

Fluorescence-labeled peptide-MHC class I multimers serve as ideal tools for the detection of antigen-specific T cells by flow cytometry, enabling functional and phenotypical characterization of specific T cells at the single cell level. While this technique offers a number of unique advantages, MHC multimer reagents can be difficult to handle in terms of stability and quality assurance. The stability of a given fluorescence-labeled MHC multimer complex depends on both the stability of the peptide-MHC complex itself and the stability of the fluorochrome. Consequently, stability is difficult to predict and long-term storage is generally not recommended. We investigated here the possibility of…

Immunoguiding, the Final Frontier in the Immunotherapy of Cancer

T cells play an important role in cancer. This notion is strongly supported by an enormous number of trials on the clinical impact of tumor-infiltrating T cells and studies consequently showing that therapeutic interventions which are based on transfer, activation and expansion, or de-blocking of tumor-specific T cells, which have met with clinical success. To optimally profit from the flow of newly developed immune-based therapeutics aiming to reinforce the systemic and local tumor-specific T-cell response, it will be required to identify biomarkers that provide the rationale to use a particular therapy, that measure the effect of intervention, and that can predict the outcome of a therape…

Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses

AbstractThe tyrosine kinase inhibitors sorafenib and sunitinib are approved for the treatment of patients with malignant diseases. To analyze the possible use of these compounds in combination with immunotherapeutic approaches, we analyzed the effects of both inhibitors on the immunostimulatory capacity of human dendritic cells (DCs) and the induction of primary immune responses in vivo. Sorafenib, but not sunitinib, inhibits function of DCs, characterized by reduced secretion of cytokines and expression of CD1a, major histocompatibility complex, and costimulatory molecules in response to TLR ligands as well as by their impaired ability to migrate and stimulate T-cell responses. These inhib…