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- Babrak, Lmar, et al.
(författare)
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Adaptive Immune Receptor Repertoire (AIRR) Community Guide to TR and IG Gene Annotation
- 2022
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Ingår i: Immunogenetics : Methods and Protocols - Methods and Protocols. - New York, NY : Springer US. - 1064-3745. - 9781071621141 - 9781071621158 ; 2453, s. 279-296
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Bokkapitel (refereegranskat)abstract
- High-throughput sequencing of adaptive immune receptor repertoires (AIRR, i.e., IG and TR) has revolutionized the ability to carry out large-scale experiments to study the adaptive immune response. Since the method was first introduced in 2009, AIRR sequencing (AIRR-Seq) has been applied to survey the immune state of individuals, identify antigen-specific or immune-state-associated signatures of immune responses, study the development of the antibody immune response, and guide the development of vaccines and antibody therapies. Recent advancements in the technology include sequencing at the single-cell level and in parallel with gene expression, which allows the introduction of multi-omics approaches to understand in detail the adaptive immune response. Analyzing AIRR-seq data can prove challenging even with high-quality sequencing, in part due to the many steps involved and the need to parameterize each step. In this chapter, we outline key factors to consider when preprocessing raw AIRR-Seq data and annotating the genetic origins of the rearranged receptors. We also highlight a number of common difficulties with common AIRR-seq data processing and provide strategies to address them.
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| 2. |
- Vollmer, Tino, et al.
(författare)
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The intratumoral CXCR3 chemokine system is predictive of chemotherapy response in human bladder cancer
- 2021
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 13:576
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Tidskriftsartikel (refereegranskat)abstract
- Chemotherapy has direct toxic effects on cancer cells; however, long-term cancer control and complete remission are likely to involve CD8+ T cell immune responses. To study the role of CD8+ T cell infiltration in the success of chemotherapy, we examined patients with muscle invasive bladder cancer (MIBC) who were categorized on the basis of the response to neoadjuvant chemotherapy (NAC). We identified the intratumoral CXCR3 chemokine system (ligands and receptor splice variants) as a critical component for tumor eradication upon NAC in MIBC. Through characterization of CD8+ T cells, we found that stem-like T cell subpopulations with abundant CXCR3alt, a variant form of the CXCL11 receptor, responded to CXCL11 in culture as demonstrated by migration and enhanced effector function. In tumor biopsies of patients with MIBC accessed before treatment, CXCL11 abundance correlated with high numbers of tumor-infiltrating T cells and response to NAC. The presence of CXCR3alt and CXCL11 was associated with improved overall survival in MIBC. Evaluation of both CXCR3alt and CXCL11 enabled discrimination between responder and nonresponder patients with MIBC before treatment. We validated the prognostic role of the CXCR3-CXCL11 chemokine system in an independent cohort of chemotherapy-treated and chemotherapy-naïve patients with MIBC from data in TCGA. In summary, our data revealed stimulatory activity of the CXCR3alt-CXCL11 chemokine system on CD8+ T cells that is predictive of chemotherapy responsiveness in MIBC. This may offer immunotherapeutic options for targeted activation of intratumoral stem-like T cells in solid tumors.
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