Abstract
In the past decade, significant progresses have taken place in the field of cancer immunotherapeutics, which are being developed for most human cancers. New immunotherapeutics, such as Ipilimumab (anti-CTLA-4), have been approved for clinical treatment; cell-based immunotherapies such as adoptive cell transfer (ACT) have either passed the final stage of human studies (e.g., Sipuleucel-T) for the treatment of selected neoplastic malignancies or reached the stage of phase II/III clinical trials. Immunotherapetics has become a sophisticated field. Multimodal therapeutic regimens comprising several functional modules (up to five in the case of ACT) have been developed to provide focused therapeutic responses with improved efficacy and reduced side-effects. However, a major challenge remains: the lack of effective and clinically applicable immune assessment methods. Due to the complexity of antitumor immune responses within patients, it is difficult to provide comprehensive assessment of therapeutic efficacy and mechanism. To address this challenge, new technologies have been developed to directly profile the cellular immune functions and the functional heterogeneity. With the goal to measure the functional proteomics of single immune cells, these technologies are informative, sensitive, high-throughput, and highly multiplex. They have been used to uncover new knowledge of cellular immune functions and have been utilized for rapid, informative, and longitudinal monitoring of immune response in clinical anti-cancer treatment. In addition, new computational tools are required to integrate high-dimensional data sets generated from the comprehensive, single cell level measurements of patient’s immune responses to guide accurate and definitive diagnostic decision. These single cell immune function assessment tools will likely contribute to new understanding of therapy mechanism, pre-treatment stratification of patients, and ongoing therapeutic monitoring and assessment.
Highlights
The field of targeted cancer therapeutics and immunotherapy has gone through significant maturation in recent years
A survey of immune cell function would require the development of high-throughput, highly multiplex single cell assays that can characterize the properties of single immune cells in producing multiple relevant effector cytokines, collectively called functional proteomics
We will focus on recent progresses in the development of single cell proteomics tools, with an emphasis on those that can be used for immune diagnostics and monitoring in cancer therapeutics
Summary
The field of targeted cancer therapeutics and immunotherapy has gone through significant maturation in recent years. Frontiers in Oncology | Tumor Immunity www.frontiersin.org of protein secretion and the non-viability of cells analyzed, this technology is less optimal for measuring cytokine production. It has been used to study the hierarchy of hematopoietic stem cell differentiation, the natural killer cell intracellular signaling and the T cell functional heterogeneity (Bendall et al, 2011; Bodenmiller et al, 2012; Newell Evan et al, 2012), as we will review later.
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