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Host-specific differences in top-expanded TCR clonotypes correlate with divergent outcomes of anti-PD-L1 treatment in responders versus non-responders

ABSTRACT: Host-specific differences in top-expanded TCR clonotypes correlate with divergent outcomes of anti-PD-L1 treatment in responders versus non-responders

PROVIDER: PRJNA944984 | ENA |

REPOSITORIES: ENA

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Host-specific differences in top-expanded TCR clonotypes correlate with divergent outcomes of anti-PD-L1 treatment in responders versus non-responders.

Project description:Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, the responses to ICI treatment are highly variable in different individuals and the underlying mechanisms remain poorly understood. Here, we employed a mouse squamous cell carcinoma (SCC) model where tumor-bearing recipients diverged into responders (R) versus non-responders (NR) upon anti-PD-L1 treatment. We performed in-depth TCRβ sequencing with immunoSEQ platform to delineate the differences in CD8 tumor-infiltrating lymphocytes (TILs). We found that R and NR CD8 TILs both exhibited evidence of clonal expansion, suggesting activation regardless of response status. We detected no differences in clonal expansion or clonal diversity indexes between R vs. NR. However, the top expanded (>1%) TCRβ clonotypes appeared to be mutually exclusive between R and NR CD8 TILs, showing a preferential expansion of distinct TCRβ clonotypes in response to the same SCC tumor in R vs. NR. Notably, the mutual exclusivity of TCR clonotypes in R vs. NR was only observed when top TCRβ clonotypes were counted, because such top-expanded clonotypes are present in the opposite outcome group at a much lower frequency. Many TCRβ sequences were detected in only one recipient at a high frequency, implicating highly individualized anti-tumor immune responses. We conclude that differences in the clonal frequency of top TCR clonotypes between R and NR CD8 TILs may be one of the factors underlying differential anti-PD-L1 responses. This notion may offer a novel explanation for variable ICI responses in different individuals, which may substantially impact the development of new strategies for personalized cancer immunotherapy.

| S-EPMC10084475 | biostudies-literature

Host-specific differences in top-expanded TCR clonotypes correlate with divergent outcomes of anti-PD-L1 treatment in responders versus non-responders

2023-03-17 | GSE227404 | GEO

A223 bintrafusp alfa non-responders and responders

Project description:A223 bintrafusp alfa non-responders and responders

| PRJNA677973 | ENA

Tear proteome of patients with non-infectious uveitis responders and non-responders to adalimumab

Project description:Proteomic anaysis of tear samples from patients with non-infectious uveitis responders and non-responders to adalimumab included in a cross-sectional study

| MSV000095892 | MassIVE

MR1-restricted T cell clonotypes are associated with “resistance” to Mycobacterium tuberculosis infection

Project description:T cells are required for protective immunity against Mycobacterium tuberculosis. We recently described a cohort of Ugandan household contacts of tuberculosis cases who appear to “resist” M. tuberculosis infection (resisters; RSTRs) and showed that these individuals harbor IFN-γ–independent T cell responses to M. tuberculosis–specific peptide antigens. However, T cells also recognize nonprotein antigens via antigen-presenting systems that are independent of genetic background, known as donor-unrestricted T cells (DURTs). We used tetramer staining and flow cytometry to characterize the association between DURTs and “resistance” to M. tuberculosis infection. Peripheral frequencies of most DURT subsets were comparable between RSTRs and latently infected controls (LTBIs). However, we observed a 1.65-fold increase in frequency of MR1-restricted T (MR1T) cells among RSTRs in comparison with LTBIs. Single-cell RNA sequencing of 18,251 MR1T cells sorted from 8 donors revealed 5,150 clonotypes that expressed a common transcriptional program, the majority of which were private. Sequencing of the T cell receptor α/T cell receptor δ (TCRα/δ) repertoire revealed several DURT clonotypes were expanded among RSTRs, including 2 MR1T clonotypes that recognized mycobacteria-infected cells in a TCR-dependent manner. Overall, our data reveal unexpected donor-specific diversity in the TCR repertoire of human MR1T cells as well as associations between mycobacteria-reactive MR1T clonotypes and resistance to M. tuberculosis infection.

2024-05-08 | GSE264592 | GEO

top-2

Project description:Caenorhabditis elegans top-2, DNA topoisomerase 2 top-2 [Source:UniProtKB/Swiss-Prot;Acc:Q23670], is differentially expressed in 4 experiment(s);

| WBGene00010785 | ExpressionAtlas

top-2

Project description:Caenorhabditis elegans top-2, DNA topoisomerase 2 top-2 [Source:UniProtKB/Swiss-Prot;Acc:Q23670], is expressed in 1 baseline experiment(s);

| WBGene00010785 | ExpressionAtlas

NCI Exceptional Responders Initiative

Project description:NCI Exceptional Responders Initiative

| PRJNA325186 | ENA

Whole blood transcriptional variations between responders and non-responders in asthma patients receiving omalizumab

Project description:To investigate blood transcriptional changes induced by omalizumab treatment and to determine variations between omalizumab responders and non-responders.

2020-07-19 | GSE134544 | GEO

A223 bintrafusp alfa non-responders and responders

Project description:Mice bearing murine A223 SCC tumors were treated with bintrafusp alfa, targeting both TGF-beta and PD-L1, then processed for single-cell sequencing to identify cell population signaling changes that characterize responders to therapy.

2021-07-23 | GSE161370 | GEO

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