The CD155/TIGIT axis promotes and maintains immune evasion in neoantigen-expressing pancreatic cancer

Freed-Pastor, William A.; Lambert, Laurens J.; Ely, Zackery A.; Pattada, Nimisha B.; Bhutkar, Arjun; Eng, George; Mercer, Kim L.; Patiño-García, Ana; Lin, Lin; Rideout, William M.; Hwang, William L.; Schenkel, Jason M.; Jaeger, Alex M.; Bronson, Roderick T.; Westcott, Peter M.K.; Hether, Tyler; Divakar, Prajan; Reeves, Jason; Deshpande, Vikram; Delorey, Toni; Phillips, Devan; Yılmaz, Ömer H.; Regev, Aviv; Jacks, Tyler

doi:10.1016/j.ccell.2021.07.007

Cited by 159 publications

(115 citation statements)

References 131 publications

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“…Male pancreatic organoids were only transplanted back into male recipients. Two genetically-defined pancreatic organoid lines were used to initiate tumors: an ex vivo transformed (KPT) line and a recently described ex vivo transformed organoid line harboring a defined neoantigen (KP;mScarletSIIN) 50 .…”

Section: Methodsmentioning

confidence: 99%

“…Autochthonous PDAC tumors were also initiated in KPT mice by retrograde pancreatic duct delivery of Ad-Ptf1a-Cre virus (7 × 10 8 pfu/mouse; University of Iowa Viral Vector Core) 27,50 . A small incision was made in the anterior abdomen (approximately 2−3 cm), the intestines and liver were gently repositioned until the biliary tree was well visualized.…”

Section: Methodsmentioning

confidence: 99%

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Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice

et al. 2021

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Existing preclinical methods for acquiring dissemination kinetics of rare circulating tumor cells (CTCs) en route to forming metastases have not been capable of providing a direct measure of CTC intravasation rate and subsequent half-life in the circulation. Here, we demonstrate an approach for measuring endogenous CTC kinetics by continuously exchanging CTC-containing blood over several hours between un-anesthetized, tumor-bearing mice and healthy, tumor-free counterparts. By tracking CTC transfer rates, we extrapolated half-life times in the circulation of between 40 and 260 s and intravasation rates between 60 and 107,000 CTCs/hour in mouse models of small-cell lung cancer (SCLC), pancreatic ductal adenocarcinoma (PDAC), and non-small cell lung cancer (NSCLC). Additionally, direct transfer of only 1−2% of daily-shed CTCs using our blood-exchange technique from late-stage, SCLC-bearing mice generated macrometastases in healthy recipient mice. We envision that our technique will help further elucidate the role of CTCs and the rate-limiting steps in metastasis.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice

et al. 2021

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“…These case studies can benefit from less biased profiling strategies in order to maximize the amount of information collected from the individual or small cohorts of samples. In addition to profiling human tissues, the GeoMx platform can be employed to characterize preclinical models [69,70]. The experimental design strategy can be adapted to study organoids or in vitro reconstructed tissue models using the same reagents that are used on human tissues.…”

Section: Profiling Across Preclinical and Clinical Samplesmentioning

confidence: 99%

Best Practices for Spatial Profiling for Breast Cancer Research with the GeoMx® Digital Spatial Profiler

Bergholtz

Carter

Cesano

et al. 2021

Cancers

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Breast cancer is a heterogenous disease with variability in tumor cells and in the surrounding tumor microenvironment (TME). Understanding the molecular diversity in breast cancer is critical for improving prediction of therapeutic response and prognostication. High-plex spatial profiling of tumors enables characterization of heterogeneity in the breast TME, which can holistically illuminate the biology of tumor growth, dissemination and, ultimately, response to therapy. The GeoMx Digital Spatial Profiler (DSP) enables researchers to spatially resolve and quantify proteins and RNA transcripts from tissue sections. The platform is compatible with both formalin-fixed paraffin-embedded and frozen tissues. RNA profiling was developed at the whole transcriptome level for human and mouse samples and protein profiling of 100-plex for human samples. Tissue can be optically segmented for analysis of regions of interest or cell populations to study biology-directed tissue characterization. The GeoMx Breast Cancer Consortium (GBCC) is composed of breast cancer researchers who are developing innovative approaches for spatial profiling to accelerate biomarker discovery. Here, the GBCC presents best practices for GeoMx profiling to promote the collection of high-quality data, optimization of data analysis and integration of datasets to advance collaboration and meta-analyses. Although the capabilities of the platform are presented in the context of breast cancer research, they can be generalized to a variety of other tumor types that are characterized by high heterogeneity.

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“…Immune checkpoint inhibition therapy has opened a new therapeutic avenue in oncology. However, only a fraction of patients will benefit so far from harnessing the immune response through the application of antibodies to inhibition checkpoint such as PDL1 or PD1, but the discovery of new checkpoints such as TGIT will offer new opportunities [85]. The utility of liquid biomarkers such as CTCs and ctDNA as prognostic and in particular predictive markers in the context of immunotherapies in solid tumors including gastrointestinal cancers have been recently reviewed in detail [86].…”

Section: Discussionmentioning

confidence: 99%

Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as a Liquid Biopsy Marker in Colorectal Cancer

Heidrich

Abdalla

Reeh

et al. 2021

Cancers

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Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. It is a heterogeneous tumor with a wide genomic instability, leading to tumor recurrence, distant metastasis, and therapy resistance. Therefore, adjunct non-invasive tools are urgently needed to help the current classical staging systems for more accurate prognostication and guiding personalized therapy. In recent decades, there has been an increasing interest in the diagnostic, prognostic, and predictive value of circulating cancer-derived material in CRC. Liquid biopsies provide direct non-invasive access to tumor material, which is shed into the circulation; this enables the analysis of circulating tumor cells (CTC) and genomic components such as circulating free DNA (cfDNA), which could provide the key for personalized therapy. Liquid biopsy (LB) allows for the identification of patients with a high risk for disease progression after curative surgery, as well as longitudinal monitoring for disease progression and therapy response. Here, we will review the most recent studies on CRC, demonstrating the clinical potential and utility of CTCs and ctDNA. We will discuss some of the advantages and limitations of LBs and the future perspectives in the field of CRC management.

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The CD155/TIGIT axis promotes and maintains immune evasion in neoantigen-expressing pancreatic cancer

Cited by 159 publications

References 131 publications

Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice

Measuring kinetics and metastatic propensity of CTCs by blood exchange between mice

Best Practices for Spatial Profiling for Breast Cancer Research with the GeoMx® Digital Spatial Profiler

Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as a Liquid Biopsy Marker in Colorectal Cancer

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