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Baseline Frequency of Inflammatory Cxcl9 Expressing Tumor-Associated Macrophages Predicts Response to Avelumab (anti-PDL-1) Treatment

ABSTRACT: scRNA-Sequencing of CD45+ TILs taken from a single tumor of a bilateral pair prior to avelumab treatment

ORGANISM(S): Mus musculus

PROVIDER: GSE150970 | GEO | 2020/05/22

REPOSITORIES: GEO

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Baseline Frequency of Inflammatory Cxcl9 Expressing Tumor-Associated Macrophages Predicts Response to Avelumab (anti-PDL-1) Treatment

Project description:Baseline Frequency of Inflammatory Cxcl9 Expressing Tumor-Associated Macrophages Predicts Response to Avelumab (anti-PDL-1) Treatment

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Project description:Local administration of IFN-α-producing proliferating myeloid cells (IFN-α-iPSC-pMCs) inhibited the tumor growth not only at the treatment site but also at the distant site (left). T cell receptor (TCR)-β chain repertoire and complementarity determining region 3 (CDR3) gene sequence analyses of tumor-infiltrating lymphocytes (TILs) showed marked enrichment of T cells with identical TCR-β chains in bilateral tumor tissues.

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Combination therapy of NHS-IL12 and avelumab enhances antitumor efficacy in preclinical cancer models

Project description:Nanostring gene expression profiling of 24 BALB/c mice bearing EMT-6 tumors under avelumab and NHS-muIL12 mono and combination therapies.

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scRNA and TCRalpha-beta-seq data from 3 dissociated renal cell carcinoma samples that were CD45 positive sorted, enriched for lymphocytes and sequenced

Project description:In our study, we have characterized the non-expanded and expanded tumor-infiltrating lymphocytes (TILs) from treatment-naive renal cell carcinoma (RCC) patients (n=3), as well as the minimally cultured pre-REP TILs and rapidly expanded REP TILs with a clinical-grade TIL expansion protocol. We observed that the REP TILs encompassed an abundance of CD4positive T-cells, together with increased LAG-3 and low PD-1 expression in the CD4positive and CD8positive T-cells. In addition, we observed that the TIL expansion protocol expanded small CD4positive T-cell clonotypes in the tumor microenvironment (TME), and that the large, exhausted tumor T-cell clonotypes do not expand. We further identified RCC-associated TCR motifs that were validated in multiple TCRalpha-beta-seq and scRNAand TCRalpha-beta-seq datasets, as well as quantified the RCC-associated TCRs from the REP protocol. Overall, the T-cells carrying the RCC-associated TCRs remained high in the tumors and corresponding pre-REP TILs, but the frequency was reduced in the REP TILs. Furthermore, the overall anti-viral TCRs remained low throughout the REP protocol. Our results provide an in-depth understanding of the origin, immunophenotype, and specificity of the TCRs in RCC TILs.

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Transcriptome differences in HCC infiltrated CD8+ T cells in effector and exhaustion state

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Project description:Host gene and protein expression impact susceptibility to clinical malaria, but the balance of immune cell populations, cytokines and genes that contributes to protection, remains incompletely understood. To identify determinants of host susceptibility to clinical malaria at a time when acquired immunity is developing, we analyzed peripheral blood mononuclear cells (PBMCs) collected from children who differed in susceptibility to clinical malaria, all from a small town in Mali. PBMCs were collected from children aged 4-6 years at the start, peak and end of the malaria season. We characterized the immune cell composition and cytokine secretion for a subset of 20 children per timepoint (10 children with no symptomatic malaria age-matched to 10 children with >2 symptomatic malarial illnesses), and gene expression patterns for six children (three per cohort) per timepoint. We noted higher frequency of HLA-DR+ CD4 T cells in protected children during the peak of the malaria season and comparable levels cytokine secretion after stimulation with malaria schizonts across all three time points. We also observed differences between the two groups of children in the expression of genes related to cell death and inflammation; in particular, inflammatory genes such as CXCL10 and STAT1 and apoptotic genes such as XAF1 were upregulated in susceptible children before the transmission season began. This suggests that differences in apoptotic and inflammatory gene expression patterns can predict susceptibility to clinical malaria.

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