T Cell Assays and MIATA: The Essential Minimum for Maximum Impact (2012)

The field of immunology has recently experienced enormous advances from which most have so far not been incorporated into standard medical practice (Davis, 2008Davis M.M. Immunity. 2008; 29: 835-838Abstract Full Text Full Text PDF PubMed Scopus (280) Google Scholar). One approach to fully exploit the existing wealth of knowledge is to implement a systematic strategy to evaluate the immune system. The potential benefit of such an approach is that it may lead to results that can be translated into the rational development of diagnostics and therapeutics (Hoos et al., 2011Hoos A. Britten C.M. Huber C. O’Donnell-Tormey J. Nat. Biotechnol. 2011; 29: 867-870Crossref PubMed Scopus (56) Google Scholar). Two prerequisites for its application are that (1) applied immune assays lead to reproducible results (van der Burg et al., 2011van der Burg S.H. Kalos M. Gouttefangeas C. Janetzki S. Ottensmeier C. Welters M.J. Romero P. Britten C.M. Hoos A. Sci. Transl. Med. 2011; 3: 08ps44Crossref Scopus (79) Google Scholar), and (2) sets of experimental results will be reported and deposited in a way that supports maximum use of data (Janetzki et al., 2009Janetzki S. Britten C.M. Kalos M. Levitsky H.I. Maecker H.T. Melief C.J. Old L.J. Romero P. Hoos A. Davis M.M. Immunity. 2009; 31: 527-528Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar; Sansone et al., 2012Sansone S.A. Rocca-Serra P. Field D. Maguire E. Taylor C. Hofmann O. Fang H. Neumann S. Tong W. Amaral-Zettler L. et al.Nat. Genet. 2012; 44: 121-126Crossref PubMed Scopus (282) Google Scholar). The task of establishing robust assays has been shown to be particularly challenging for cellular assays. This has led to multiple independent activities to harmonize and standardize immune assays (van der Burg et al., 2011van der Burg S.H. Kalos M. Gouttefangeas C. Janetzki S. Ottensmeier C. Welters M.J. Romero P. Britten C.M. Hoos A. Sci. Transl. Med. 2011; 3: 08ps44Crossref Scopus (79) Google Scholar; Maecker et al., 2010Maecker H.T. McCoy Jr., J.P. Amos M. Elliott J. Gaigalas A. Wang L. Aranda R. Banchereau J. Boshoff C. Braun J. et al.FOCIS Human Immunophenotyping ConsortiumNat. Immunol. 2010; 11: 975-978Crossref PubMed Scopus (110) Google Scholar; Roep et al., 2012Roep B.O. Buckner J. Sawcer S. Toes R. Zipp F. Nat. Med. 2012; 18: 48-53Crossref PubMed Scopus (44) Google Scholar). Experiments conducted by more than 100 labs showed that (1) a plethora of different protocols exists, (2) results generated across institutions vary greatly, (3) multiple process steps contribute to test variation, (4) many labs performing T cell assays do not control critical process steps, and (5) the majority of reports comprising results from T cell assay experiments lack critical information. At first these findings were met with skepticism, given that they seemed to contradict promising results showing that cellular assays can constitute robust tools to quantify antigen-specific T cell responses. However, both the optimistic and the pessimistic view have validity. T cell assays can deliver compelling performance in the hands of skilled researchers. Nonetheless, pulling data from heterogeneous groups of labs demonstrates that controlling the performance of cellular assays requires explicit knowledge of their critical protocol details. Notably, publications lacking those critical protocol details may be difficult to interpret and to reproduce. Such reporting issues have the potential to hamper progress in the field. To provide a solution, the Minimal Information about T Cell Assays (MIATA) project was initiated in 2009 (Janetzki et al., 2009Janetzki S. Britten C.M. Kalos M. Levitsky H.I. Maecker H.T. Melief C.J. Old L.J. Romero P. Hoos A. Davis M.M. Immunity. 2009; 31: 527-528Abstract Full Text Full Text PDF PubMed Scopus (163) Google Scholar) as a field-spanning initiative whose main objective is to generate a broadly acceptable framework for the reporting of results from commonly used T cell assays, which is envisioned to be expandable to new, complex assays (Sharma et al., 2011Sharma P. Wagner K. Wolchok J.D. Allison J.P. Nat. Rev. Cancer. 2011; 11: 805-812Crossref PubMed Scopus (498) Google Scholar; for a full list of MIATA contributors, see http://www.miataproject.org/index.php?option=com_content&view=article&id=4&Itemid=6). The generated MIATA guidelines presented here are the outcome of one of the most intensive community-wide vetting processes in the field of immunology so far (Britten et al., 2011Britten C.M. Janetzki S. van der Burg S.H. Huber C. Kalos M. Levitsky H.I. Maecker H.T. Melief C.J. O’Donnell-Tormey J. Odunsi K. et al.Cancer Immunol. Immunother. 2011; 60: 15-22Crossref PubMed Scopus (56) Google Scholar). This process and all its steps are transparently displayed at the project’s website (www.miataproject.org). Importantly, MIATA is not about implementing standardization rules on how to perform a T cell assay nor does the project promote any specific reagents or protocols. MIATA offers minimum criteria for consistent reporting of T cell assay results to increase data interpretability and experimental reproducibility across the scientific community. Consequently, the current version of MIATA is a testimonial to the freedom and transparency of research and proves the ability of the research community to form consensus on critical variables affecting the quality of their work. Laboratories performing immunological monitoring come in different flavors. On one hand, there are research labs that apply immune assays in a flexible way to conduct high-quality research. On the other hand, there are specialized core labs with the main focus on the tightly controlled performance of a selected portfolio of immune assays. The MIATA community acknowledges that both categories of labs are crucial as they harbor complementary expertise needed to achieve progress in research and development and that a reporting framework does not discredit any data set that was not generated in a certified lab using a fully standardized or validated assay. The MIATA guidelines are divided into modules and submodules for easy referencing (Table S1). The modules address critical information about:1.the sample,2.the assay,3.the acquisition strategy,4.the (interpretation of) raw data, and5.the laboratory environment. The MIATA website provides the guidelines as well as sample reports for the following assays: intracellular cytokine staining, HLA-peptide multimer staining, and Elispot. It further lists supplementary information including relevant publications and definitions. Adherence to MIATA guidelines is expected to enhance consistency of data reporting across laboratories and increase data reproducibility. As such, it is recommended to be used broadly within the community. We propose that adherence to MIATA is optional. One envisioned concept to implement MIATA is that investigators submitting a research article may choose to indicate whether their article adheres to MIATA. This can be accompanied by the executed checklist available from the website. Journals may additionally confirm via peer review that all five MIATA modules were sufficiently addressed, leading to an official statement on MIATA compliance in the article. Such a statement will eventually be regarded as a “label of honor” and a quality measure for the published work. Depending on the adoption rate in the scientific community, reporting using MIATA might become a routine practice that was not enforced from top down but achieved in a bottom-up approach. MIATA’s promise is to offer more consistent and transparent reporting of T cell experiments in scientific publications making it easier to interpret and reproduce published methods and data sets. In addition, broad implementation of MIATA might foster a stepwise increase of the quality of applied immune assays due to increased awareness of the critical components impacting on test performance. Accomplishing this mission requires commitment from each member of the immune monitoring community and support of journals to encourage but not force authors to report according to MIATA. The large number of experts from different fields of immunology that actively contributed to mature the project is an indication of the high interest in such guidelines. MIATA is ready for embracement by the immunology community at large. Download .pdf (.08 MB) Help with pdf files Document S1. Table S1