Ligand-mediated PAI-1 inhibition in a mouse model of peritoneal carcinomatosis

Hendrikson, Josephine; Liu, Ying; Ng, Wai Har; Lee, Jing Yi; Lim, Abner Herbert; Loh, Jui Wan; Ng, Cedric Chuan‐Young; Ong, Whee Sze; Tan, Joey Wee-Shan; Tan, Qiu Xuan; Ng, Gillian; Shannon, Nicholas B.; Lim, Weng Khong; Lim, Tony Kiat-Hon; Chua, Clarinda; Wong, Jolene Si Min; Tan, Grace Hwei Ching; So, Jimmy Bok Yan; Yeoh, Khay Guan; Teh, Bin Tean; Chia, Claramae Shulyn; Soo, Khee Chee; Kon, Oi Lian; Tan, Iain Beehuat; Chan, Jason Yongsheng; Teo, Melissa Ching Ching; Ong, Chin-Ann Johnny

doi:10.1016/j.xcrm.2022.100526

Cited by 10 publications

(14 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Stimulated lymph node samples (CRC) had been obtained previously ( 5 ), while PBMCs from the HCC patient were stimulated following the same procedure ( 5 ) prior to analysis (Supplementary Materials). Single-cell sequencing used Chromium Single Cell 5’ and 3′ Reagent Kits v2 and v3 (10× Genomics, San Francisco, CA, USA) ( 21 ), while paired-end sequencing (2×150 bp) was performed using the NovaSeq 6000 platform (Illumina, Inc., San Diego, CA, USA) (Supplementary Materials; bioinformatic analysis is depicted in Supplementary Figure 1B ). Marker genes for the B cell phenotypes were identified by comparing SARS-CoV-2-stimulated and unstimulated samples (using the FindMarkers function in Seurat; Supplementary Table 3 ).…”

Section: Case Descriptionmentioning

confidence: 99%

Case report: Understanding the impact of persistent tissue-localization of SARS-CoV-2 on immune response activity via spatial transcriptomic analysis of two cancer patients with COVID-19 co-morbidity

et al. 2022

Self Cite

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected half a billion people, including vulnerable populations such as cancer patients. While increasing evidence supports the persistence of SARS-CoV-2 months after a negative nasopharyngeal swab test, the effects on long-term immune memory and cancer treatment are unclear. In this report, we examined post-COVID-19 tissue-localized immune responses in a hepatocellular carcinoma (HCC) patient and a colorectal cancer (CRC) patient. Using spatial whole-transcriptomic analysis, we demonstrated spatial profiles consistent with a lymphocyte-associated SARS-CoV-2 response (based on two public COVID-19 gene sets) in the tumors and adjacent normal tissues, despite intra-tumor heterogeneity. The use of RNAscope and multiplex immunohistochemistry revealed that the spatial localization of B cells was significantly associated with lymphocyte-associated SARS-CoV-2 responses within the spatial transcriptomic (ST) niches showing the highest levels of virus. Furthermore, single-cell RNA sequencing data obtained from previous (CRC) or new (HCC) ex vivo stimulation experiments showed that patient-specific SARS-CoV-2 memory B cells were the main contributors to this positive association. Finally, we evaluated the spatial associations between SARS-CoV-2-induced immunological effects and immunotherapy-related anti-tumor immune responses. Immuno-predictive scores (IMPRES) revealed consistent positive spatial correlations between T cells/cytotoxic lymphocytes and the predicted immune checkpoint blockade (ICB) response, particularly in the HCC tissues. However, the positive spatial correlation between B cells and IMPRES score was restricted to the high-virus ST niche. In addition, tumor immune dysfunction and exclusion (TIDE) analysis revealed marked T cell dysfunction and inflammation, alongside low T cell exclusion and M2 tumor-associated macrophage infiltration. Our results provide in situ evidence of SARS-CoV-2-generated persistent immunological memory, which could not only provide tissue protection against reinfection but may also modulate the tumor microenvironment, favoring ICB responsiveness. As the number of cancer patients with COVID-19 comorbidity continues to rise, improved understanding of the long-term immune response induced by SARS-CoV-2 and its impact on cancer treatment is much needed.

show abstract

Section: Case Descriptionmentioning

confidence: 99%

Case report: Understanding the impact of persistent tissue-localization of SARS-CoV-2 on immune response activity via spatial transcriptomic analysis of two cancer patients with COVID-19 co-morbidity

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…The protocol below details the process of establishing PDADX mouse models using malignant ascites from patients with PC as well as the utility of the model to evaluate drug efficacy. For example, we generated PDADX models of colorectal PC origin to evaluate susceptibility to the inhibition of a paracrine factor in ascites ( Hendrikson et al., 2022 ). This protocol can be adapted for the establishment of mouse models of any histological subtype of PC (primary, colorectal, gastric, ovarian, etc.…”

Section: Before You Beginmentioning

confidence: 99%

“…In addition, the cellular component of ascites contains a heterogenous mixture of cancer cells and stromal cells including epithelial / mesothelial cells, fibroblasts, adipocytes, and inflammatory cells ( Hendrikson et al., 2022 ; Kim et al., 2016 ), which will form PDADX tumors with complex compositions. Although the cancer cells in PDADX tumors should exhibit similar genomic and morphological features to the matched patient’s cancer cells, variation in the compositions of different cell types generated in the process of tumor development are unavoidable among different PDADX passages and mice, which may lead to fluctuations in tumor burden when performing drug efficacy experiments.…”

Section: Limitationsmentioning

confidence: 99%

“…By serving as a proxy, PDADX models represent a valuable tool for preclinical testing of new therapeutics for PC. For complete details on the use and execution of this protocol, please refer to Hendrikson et al. (2022) .…”

mentioning

confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to Hendrikson et al. (2022) .…”

mentioning

confidence: 99%

See 2 more Smart Citations

Generating patient-derived ascites-dependent xenograft mouse models of peritoneal carcinomatosis

Liu

Zhu

et al. 2022

STAR Protocols

Self Cite

View full text Add to dashboard Cite

Synergy and Coordination Between Biomimetic Nanoparticles and Biological Cells/Tissues/Organs/Systems: Applications in Nanomedicine and Prospect

Issaka

Wariboko

Agyekum

2023

Biomedical Materials & Devices

View full text Add to dashboard Cite

Ligand-mediated PAI-1 inhibition in a mouse model of peritoneal carcinomatosis

Cited by 10 publications

References 74 publications

Case report: Understanding the impact of persistent tissue-localization of SARS-CoV-2 on immune response activity via spatial transcriptomic analysis of two cancer patients with COVID-19 co-morbidity

Case report: Understanding the impact of persistent tissue-localization of SARS-CoV-2 on immune response activity via spatial transcriptomic analysis of two cancer patients with COVID-19 co-morbidity

Generating patient-derived ascites-dependent xenograft mouse models of peritoneal carcinomatosis

Synergy and Coordination Between Biomimetic Nanoparticles and Biological Cells/Tissues/Organs/Systems: Applications in Nanomedicine and Prospect

Contact Info

Product

Resources

About