Layilin augments integrin activation to promote antitumor immunity

Mahuron, Kelly; Moreau, Joshua M.; Glasgow, Jeff E.; Boda, Devi P; Pauli, Mariela; Gouirand, Victoire; Panjabi, Luv; Grewal, Robby; Luber, Jacob M.; Mathur, Anubhav N.; Feldman, R. M. Renny; Shifrut, Eric; Mehta, Pooja; Lowe, Margaret M.; Alvarado, Michael; Marson, Alexander; Singer, Meromit; Wells, J. Vivian; Jupp, Ray; Daud, Adil; Rosenblum, Michael D.

doi:10.1084/jem.20192080

Cited by 41 publications

(46 citation statements)

References 48 publications

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“…To confirm the presence of MAIT cells in the metastasis and primary tumor site we analyzed a public dataset available on Gene Expression Omnibus (GSE148190) 26 . This dataset contains single-cell RNA and TCR sequencing of PBMCs and tumor-infiltrating lymphocytes from untreated patients with metastatic melanoma.…”

Section: Resultsmentioning

confidence: 99%

Circulating mucosal-associated invariant T cells identify patients responding to anti-PD-1 therapy

et al. 2021

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Immune checkpoint inhibitors are used for treating patients with metastatic melanoma. Since the response to treatment is variable, biomarkers are urgently needed to identify patients who may benefit from such therapy. Here, we combine single-cell RNA-sequencing and multiparameter flow cytometry to assess changes in circulating CD8+ T cells in 28 patients with metastatic melanoma starting anti-PD-1 therapy, followed for 6 months: 17 responded to therapy, whilst 11 did not. Proportions of activated and proliferating CD8+ T cells and of mucosal-associated invariant T (MAIT) cells are significantly higher in responders, prior to and throughout therapy duration. MAIT cells from responders express higher level of CXCR4 and produce more granzyme B. In silico analysis support MAIT presence in the tumor microenvironment. Finally, patients with >1.7% of MAIT among peripheral CD8+ population show a better response to treatment. Our results thus suggest that MAIT cells may be considered a biomarker for patients responding to anti-PD-1 therapy.

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Section: Resultsmentioning

confidence: 99%

Circulating mucosal-associated invariant T cells identify patients responding to anti-PD-1 therapy

et al. 2021

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“…The gene expression scRNAseq data for patients K409 and K411 (initial blood/tumor pair) and the TCR data (for tumor) can be found on GEO with accession no. GSE148190 ( Mahuron et al, 2020 ). The scRNAseq generated during this study can be found on GEO as a SuperSeries with accession no.…”

Section: Methodsmentioning

confidence: 99%

Single-cell analyses identify circulating anti-tumor CD8 T cells and markers for their enrichment

Pauken

Shahid

Lagattuta

et al. 2021

Journal of Experimental Medicine

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The ability to monitor anti-tumor CD8+ T cell responses in the blood has tremendous therapeutic potential. Here, we used paired single-cell RNA and TCR sequencing to detect and characterize “tumor-matching” (TM) CD8+ T cells in the blood of mice with MC38 tumors or melanoma patients using the TCR as a molecular barcode. TM cells showed increased activation compared with nonmatching T cells in blood and were less exhausted than matching cells in tumors. Importantly, PD-1, which has been used to identify putative circulating anti-tumor CD8+ T cells, showed poor sensitivity for identifying TM cells. By leveraging the transcriptome, we identified candidate cell surface markers for TM cells in mice and patients and validated NKG2D, CD39, and CX3CR1 in mice. These data show that the TCR can be used to identify tumor-relevant cells for characterization, reveal unique transcriptional properties of TM cells, and develop marker panels for tracking and analysis of these cells.

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“…This study did not generate new unique reagents. The gene expression scRNA seq data for patients K409 and K411 (initial blood/tumor pair) and the TCR data (for K409 tumor) can be found on GEO with accession number GSE148190 (Mahuron et al, 2020). The scRNA-seq data generated during this study will be made available upon publication.…”

Section: Resource Availabilitymentioning

confidence: 99%

Single-cell analyses identify circulating anti-tumor CD8 T cells and markers for their enrichment

Pauken

Shahid

Lagattuta

et al. 2020

Preprint

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The ability to monitor anti-tumor CD8+ T cell responses in the blood has tremendous therapeutic potential. Here, we used paired single-cell RNA sequencing and T cell receptor (TCR) sequencing to detect and characterize tumor matching (TM) CD8+ T cells in the blood of mice with MC38 tumors and melanoma patients using the TCR as a molecular barcode. TM cells showed increased activation compared to non-matching T cells in blood, and appeared less exhausted than matching counterparts in tumor. Importantly, PD-1, which has been used to identify putative circulating anti-tumor CD8+ T cells, showed poor sensitivity for identifying TM cells. By leveraging the transcriptome we identified candidate cell surface marker panels for TM cells in mice and melanoma patients, and validated NKG2D, CD39, and CX3CR1 in mice. These data demonstrate that the TCR can be used to identify tumor-relevant populations for comprehensive characterization, reveal unique transcriptional properties of TM cells, and develop marker panels for tracking and analysis of these cells.

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Layilin augments integrin activation to promote antitumor immunity

Cited by 41 publications

References 48 publications

Circulating mucosal-associated invariant T cells identify patients responding to anti-PD-1 therapy

Circulating mucosal-associated invariant T cells identify patients responding to anti-PD-1 therapy

Single-cell analyses identify circulating anti-tumor CD8 T cells and markers for their enrichment

Single-cell analyses identify circulating anti-tumor CD8 T cells and markers for their enrichment

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