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Huuhtanen, J.

Publications and source records attributed to Huuhtanen, J..

2 recordsLinked to original sources

TCRGP: Determining epitope specificity of T cell receptors

T cell receptors (TCRs) can recognize various pathogens and consequently start immune responses. TCRs can be sequenced from individuals and methods analyzing the specificity of the TCRs can help us better understand individuals immune status in different diseases. We have developed TCRGP, a novel Gaussian process method to predict if TCRs recognize certain epitopes. This method can utilize CDR sequences from TCR and TCR{beta} chains and learn which CDRs are important in recognizing different epitopes. We have experimented with with epitope-specific data against 29 epitopes and performed a comprehensive evaluation with existing prediction methods. On this data, TCRGP outperforms other state-of-the-art methods in epitope-specificity predictions. We also propose a novel analysis approach for combined single-cell RNA and TCR{beta} (scRNA+TCR{beta}) sequencing data by quantifying epitope-specific TCRs with TCRGP in phenotypes identified from scRNA-seq data. With this approach, we find HBV-epitope specific T cells and their transcriptomic states in hepatocellular carcinoma patients.

bioinformatics

Single-cell RNA sequencing reveals a dynamic stromal niche within the evolving tumour microenvironment

Non-cancerous stromal cells represent a highly diverse compartment of the tumour, yet their role across tumour evolution remains unclear. We employed single-cell RNA sequencing to determine stromal adaptations in murine melanoma at different points of tumour development. Naive lymphocytes recruited from lymph nodes underwent activation and clonal expansion within the tumour, prior to PD1 and Lag3 expression, while tumour-associated myeloid cells promoted the formation of a suppressive niche through cytokine secretion and inhibitory T cell interactions. We identified three temporally distinct cancer-associated fibroblast (CAF) populations displaying unique signatures, and verified these in human datasets. In early tumours, immune CXCL12/CSF1 and complement-expressing CAFs supported recruitment of macrophages, whereas contractile CAFs became more prevalent in later tumours. This study highlights the complex interplay and increasing diversity among cells that co-evolve with the tumour, indicating that from early stages of development, stromal cells acquire the capacity to modulate the immune landscape towards suppression.

cancer biology