A tumor-microenvironment fully responsive nano-platform for MRI-guided photodynamic and photothermal synergistic therapy

Multifunctional biomimetic nanozyme (SSMA/DOX) is fabricated, which enables tumor microenvironment responsive self-cascade catalysis to reach MRI guided enhanced chemo/chemodynamic therapy.

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Next Generation Imaging Techniques to Define Immune Topographies in Solid Tumors

Frontiers in Immunology ◽

10.3389/fimmu.2020.604967 ◽

2021 ◽

Vol 11 ◽

Author(s):

Violena Pietrobon ◽

Alessandra Cesano ◽

Francesco Marincola ◽

Jakob Nikolas Kather

Keyword(s):

Tumor Microenvironment ◽

Solid Tumors ◽

Imaging Techniques ◽

Temporal Distribution ◽

Quantitative Information ◽

Patient Specific ◽

Next Generation ◽

Current Standard ◽

Immune Exclusion ◽

New Biomarkers

In recent years, cancer immunotherapy experienced remarkable developments and it is nowadays considered a promising therapeutic frontier against many types of cancer, especially hematological malignancies. However, in most types of solid tumors, immunotherapy efficacy is modest, partly because of the limited accessibility of lymphocytes to the tumor core. This immune exclusion is mediated by a variety of physical, functional and dynamic barriers, which play a role in shaping the immune infiltrate in the tumor microenvironment. At present there is no unified and integrated understanding about the role played by different postulated models of immune exclusion in human solid tumors. Systematically mapping immune landscapes or “topographies” in cancers of different histology is of pivotal importance to characterize spatial and temporal distribution of lymphocytes in the tumor microenvironment, providing insights into mechanisms of immune exclusion. Spatially mapping immune cells also provides quantitative information, which could be informative in clinical settings, for example for the discovery of new biomarkers that could guide the design of patient-specific immunotherapies. In this review, we aim to summarize current standard and next generation approaches to define Cancer Immune Topographies based on published studies and propose future perspectives.

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A novel patient derived orthotopic xenograft model of gastro-esophageal junction cancer: Key platform for translational discoveries.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.64 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 64-64

Author(s):

Omkara Lakshmi Veeranki

Keyword(s):

Next Generation Sequencing ◽

Tumor Microenvironment ◽

Gastroesophageal Junction ◽

Lymphatic Vessels ◽

Xenograft Model ◽

Inflammatory Cells ◽

Next Generation ◽

Orthotopic Xenograft ◽

Generation Sequencing ◽

Efficacy Studies

64 Background: Mouse models of gastroesophageal junction (GEJ) cancer strive to recapitulate the intratumoral heterogeneity and cellular crosstalk within patient tumors to improve clinical translation. Current GEJ models have limited applications in tumor microenvironment, immune oncology and metastatic studies. Methods: A novel patient derived tumor orthotopic xenograft (PDOX) was established from GEJ cancer via surgical implantation. Patient tumor was compared to subcutaneously implanted PDX and PDOX by H&E, IHC, and next generation sequencing (T200.1 panel). Drug efficacy studies of 5-flurouracil with and without radiotherapy are being performed. Results: Mechanical abrasion of mouse GEJ prior to implantation of patient derived tumor in situ promotes tumor engraftment (100%, n = 6). Complete PDOX engraftment was observed with rapid intra and extra luminal tumor growth as evidenced by MRI. Patient derived stroma co-engrafts with tumor cells in GEJ-PDOX. PDOXs contain fibroblasts, immune and inflammatory cells, vascular and lymphatic vessels. Stromal hallmarks of aggressive GEJs are recapitulated in GEJ-PDOX mouse model. PDOXs demonstrates tumor invasion into vasculature. GEJ-PDOXs is a clinically relevant model for metastases and immunological studies. Next generation sequencing with the T200.1 revealed that the loss of heterozygosity of NOTCH3, TGFβ1, EZH2, and MLL3 are maintained with similar allelic frequency between the patient tumor and the xenografts. Additional somatic SNVs such as ARID1A, NSD1 (CDS157-158), NSD1 (CDS158-159), KDM6A, XPO1, MAPK1 and EGFR were found to be acquired in xenograft tumor tissues that were not observed in patient tumor. Drug and radiation efficacy studies are ongoing, tumor response to radiation was observed. Conclusions: A GEJ-PDOX model exhibits remarkable fidelity to human disease and captures the precise tissue microenvironment present within the local GEJ architecture facilitating it as a novel tool in translating to clinics. This model can be applied to address importance of tumor microenvironment in metastatic and immunological studies, and to develop novel therapeutic approaches for the treatment of GEJ cancer.

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Next-Generation Digital Histopathology of the Tumor Microenvironment

Genes ◽

10.3390/genes12040538 ◽

2021 ◽

Vol 12 (4) ◽

pp. 538

Author(s):

Felicitas Mungenast ◽

Achala Fernando ◽

Robert Nica ◽

Bogdan Boghiu ◽

Bianca Lungu ◽

...

Keyword(s):

Tumor Microenvironment ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Imaging Techniques ◽

Image Cytometry ◽

Automated Analysis ◽

Next Generation ◽

Cellular Markers ◽

Cellular Phenotypes ◽

Cancer Tissues

Progress in cancer research is substantially dependent on innovative technologies that permit a concerted analysis of the tumor microenvironment and the cellular phenotypes resulting from somatic mutations and post-translational modifications. In view of a large number of genes, multiplied by differential splicing as well as post-translational protein modifications, the ability to identify and quantify the actual phenotypes of individual cell populations in situ, i.e., in their tissue environment, has become a prerequisite for understanding tumorigenesis and cancer progression. The need for quantitative analyses has led to a renaissance of optical instruments and imaging techniques. With the emergence of precision medicine, automated analysis of a constantly increasing number of cellular markers and their measurement in spatial context have become increasingly necessary to understand the molecular mechanisms that lead to different pathways of disease progression in individual patients. In this review, we summarize the joint effort that academia and industry have undertaken to establish methods and protocols for molecular profiling and immunophenotyping of cancer tissues for next-generation digital histopathology—which is characterized by the use of whole-slide imaging (brightfield, widefield fluorescence, confocal, multispectral, and/or multiplexing technologies) combined with state-of-the-art image cytometry and advanced methods for machine and deep learning.

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