dc.contributor.author | Hoover, Ashley R. | |
dc.contributor.author | Liu, Kaili | |
dc.contributor.author | DeVette, Christa I. | |
dc.contributor.author | Krawic, Jason R. | |
dc.contributor.author | Medcalf, Alexandra D. | |
dc.contributor.author | West, Connor L. | |
dc.contributor.author | Hode, Tomas | |
dc.contributor.author | Lam, Samuel S.K. | |
dc.contributor.author | Welm, Alana L. | |
dc.contributor.author | Sun, Xiao-Hong | |
dc.contributor.author | Hildebrand, William H. | |
dc.contributor.author | Chen, Wei R. | |
dc.date.accessioned | 2022-09-02T15:48:25Z | |
dc.date.available | 2022-09-02T15:48:25Z | |
dc.date.issued | 2022-06-05 | |
dc.identifier.citation | Hoover, AR, Liu, K, DeVette, CI, et al. Single-cell RNA sequencing reveals localized tumour ablation and intratumoural immunostimulant delivery potentiate T cell mediated tumour killing. Clin Transl Med. 2022; 12:e937. https://doi.org/10.1002/ctm2.937 | en_US |
dc.identifier.uri | https://hdl.handle.net/11244/336518 | |
dc.description.abstract | Background: Metastatic breast cancer poses great challenge in cancer treatment. N-dihydrogalactochitosan (GC) is a novel immunoadjuvant that stimulates systemic immune responses when administered intratumourally following local tumour ablation. A combination of photothermal therapy (PTT) and GC, referred to as localized ablative immunotherapy (LAIT), extended animal survival and generates an activated B cell phenotype in MMTV-PyMT mouse mammary tumour microenvironment (TME). However, how T cell populations respond to LAIT remains to be elucidated. | en_US |
dc.description.abstract | Methods: Using depletion antibodies, we studied the contributions of CD8+ and CD4+ T cells to the therapeutic effect of LAIT. Using single-cell RNA-sequencing (scRNAseq), we analysed tumour-infiltrating T cell heterogeneity and dissected their transcriptomes upon treatments of PTT, GC, and LAIT (PTT+GC). | |
dc.description.abstract | Results: Loss of CD8+ T cells after LAIT abrogated the therapeutic benefits of LAIT. Ten days after treatment, proportions of CD8+ and CD4+ T cells in untreated TME were 19.2% and 23.0%, respectively. Upon LAIT, both proportions were increased to 25.5% and 36.2%, respectively. In particular, LAIT increased the proportions of naïve and memory cells from a resting state to an activated state. LAIT consistently induced the expression of co-stimulatory molecules, type I IFN responsive genes, and a series of antitumor cytokines, Ifng, Tnf, Il1, and Il17 in CD8+ and CD4+ T cells. LAIT also induced immune checkpoints Pdcd1, Ctla4, and Lag3 expression, consistent with T cell activation. Relevant to clinical translation, LAIT also upregulated genes in CD8+and CD4+T cells that positively correlated with extended survival of breast cancer patients. | |
dc.description.abstract | Conclusions: Overall, our results reveal that LAIT prompts immunological remodelling of T cells by inducing broad proinflammatory responses and inhibiting suppressive signalling to drive antitumour immunity. | |
dc.description.sponsorship | Financial support was provided by the University of Oklahoma Libraries’ Open Access Fund. National Cancer Institute, Grant/AwardNumbers: R01CA205348, R01CA269897;Oklahoma Center for the Advancement ofScience and Technology, Grant/AwardNumbers: HR16-085, HF20-019. | en_US |
dc.language | en_US | en_US |
dc.rights | Attribution 4.0 International | * |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | antitumor immune response | en_US |
dc.subject | ocalized ablative immunotherapy (LAIT) | en_US |
dc.subject | mouse mammarytumour virus-polyoma middle T (MMTV-PyMT) | en_US |
dc.subject | N-dihydrogalactochitosan (GC) | en_US |
dc.subject | photothermal therapy (PTT) | en_US |
dc.subject | single-cell RNA sequencing (scRNAseq) | en_US |
dc.subject | tumour-infiltrating T cells | en_US |
dc.title | Single-cell RNA sequencing reveals localized tumourablation and intratumoural immunostimulant deliverypotentiate T cell mediated tumour killing | en_US |
dc.type | Article | en_US |
dc.description.peerreview | Yes | en_US |
dc.identifier.doi | 10.1002/ctm2.937 | en_US |
ou.group | Gallogly College of Engineering::Stephenson School of Biomedical Engineering | en_US |