Enriched cancer stem cells, dense stroma, and cold immunity: Interrelated events in pancreatic cancer

Mortezaee, Keywan

doi:10.1002/jbt.22708

Cited by 75 publications

(39 citation statements)

References 60 publications

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“…[ 31 ] Tumor ECs are another cell type that represents cytogenetic abnormalities including multiple centrosomes, multiple chromosomes, and aneuploidy that render them resistance to antiangiogenic modalities. [ 217 ] It is worthy to note that CAFs [ 216,218 ] and CSCs [ 219 ] are both heterogeneous cell populations, which may infer that heterogeneity is not essentially an indicator of a cellular genomic state.…”

Section: Key Considerations In Regard To Solid Tumors and Therapymentioning

confidence: 99%

The current knowledge concerning solid cancer and therapy

Najafi

Majidpoor

Toolee

et al. 2021

J Biochem & Molecular Tox

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Solid cancers comprise a large number of new cases and deaths from cancer each year globally. There are a number of strategies for addressing tumors raised from solid organs including surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, combinational therapy, and stem cell and extracellular vesicle (EV) therapy. Surgery, radiotherapy, and chemotherapy are the dominant cures, but are not always effective, in which even in a localized tumor there is a possibility of tumor relapse after surgical resection. Over half of the cancer patients will receive radiotherapy as a part of their therapeutic schedule. Radiotherapy can cause an abscopal response for boosting the activity of the immune system outside the local field of radiation, but it may also cause an unwanted bystander effect, predisposing nonradiated cells into carcinogenesis. In the context of immunotherapy, immune checkpoint inhibition is known as the standard‐of‐care, but the major concern is in regard with cold cancers that show low responses to such therapy. Stem‐cell therapy can be used to send prodrugs toward the tumor area; this strategy, however, has its own predicaments, such as unwanted attraction toward the other sites including healthy tissues and its instability. A substitute to such therapy and quite a novel strategy is to use EVs, by virtue of their stability and potential to cross biological barriers and long‐term storage of contents. Combination therapy is the current focus. Despite advances in the field, there are still unmet concerns in the area of effective cancer therapy, raising challenges and opportunities for future investigations.

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Section: Key Considerations In Regard To Solid Tumors and Therapymentioning

confidence: 99%

The current knowledge concerning solid cancer and therapy

Najafi

Majidpoor

Toolee

et al. 2021

J Biochem & Molecular Tox

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“…The TME promotes tumor stem cell renewal, proliferation, invasion, and angiogenesis while creating an immunosuppressive environment (Nicholas et al, 2016;Najafi et al, 2019). In solid tumors, dense stromal collagen (desmoplasia) creates a physical barrier that supports cancer growth, in part by promoting hypoxia and precluding entry of immune cells into the tumor mass while maintaining blood vessels that allow tumor cells to metastasize (Mortezaee, 2021), a particularly common feature of pancreatic cancer (Bulle and Lim, 2020). Other components of the TME, such as tumorassociated macrophages (TAMs) (Vitale et al, 2019) and intercellular signals such as IL10 (Ouyang and O'Garra, 2019) and TGF-β (Ganesh and Massagué, 2018) represent therapeutic targets responsible for primary resistance to immune checkpoint blockade (Bulle and Lim, 2020).…”

Section: Immunotherapy the Tumor Microenvironment And Multiplex Stainingmentioning

confidence: 99%

Tissue Multiplex Analyte Detection in Anatomic Pathology – Pathways to Clinical Implementation

Wharton¹,

Wood²,

Manesse³

et al. 2021

Front. Mol. Biosci.

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Background: Multiplex tissue analysis has revolutionized our understanding of the tumor microenvironment (TME) with implications for biomarker development and diagnostic testing. Multiplex labeling is used for specific clinical situations, but there remain barriers to expanded use in anatomic pathology practice.Methods: We review immunohistochemistry (IHC) and related assays used to localize molecules in tissues, with reference to United States regulatory and practice landscapes. We review multiplex methods and strategies used in clinical diagnosis and in research, particularly in immuno-oncology. Within the framework of assay design and testing phases, we examine the suitability of multiplex immunofluorescence (mIF) for clinical diagnostic workflows, considering its advantages and challenges to implementation.Results: Multiplex labeling is poised to radically transform pathologic diagnosis because it can answer questions about tissue-level biology and single-cell phenotypes that cannot be addressed with traditional IHC biomarker panels. Widespread implementation will require improved detection chemistry, illustrated by InSituPlex technology (Ultivue, Inc., Cambridge, MA) that allows coregistration of hematoxylin and eosin (H&E) and mIF images, greater standardization and interoperability of workflow and data pipelines to facilitate consistent interpretation by pathologists, and integration of multichannel images into digital pathology whole slide imaging (WSI) systems, including interpretation aided by artificial intelligence (AI). Adoption will also be facilitated by evidence that justifies incorporation into clinical practice, an ability to navigate regulatory pathways, and adequate health care budgets and reimbursement. We expand the brightfield WSI system “pixel pathway” concept to multiplex workflows, suggesting that adoption might be accelerated by data standardization centered on cell phenotypes defined by coexpression of multiple molecules.Conclusion: Multiplex labeling has the potential to complement next generation sequencing in cancer diagnosis by allowing pathologists to visualize and understand every cell in a tissue biopsy slide. Until mIF reagents, digital pathology systems including fluorescence scanners, and data pipelines are standardized, we propose that diagnostic labs will play a crucial role in driving adoption of multiplex tissue diagnostics by using retrospective data from tissue collections as a foundation for laboratory-developed test (LDT) implementation and use in prospective trials as companion diagnostics (CDx).

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“…ICI monotherapy has no effect on pancreatic ductal adenocarcinoma (PDAC). Thus, the functionality of infiltrated T cells is more important than the infiltration rate (Majidpoor & Mortezaee, 2021b; Mortezaee, 2021a). To explain, tumors like breast, ovary, prostate, pancreas, and colorectal cancer (CRC) are generally placed into the category of cold immunity.…”

Section: Cells and Signaling Of The Tme And The Characteristics Of An Abnormal Stromal Bed In A Tumormentioning

confidence: 99%

“…This is indicative of the importance of abnormality in the fibroblastic cell content for tumor progression. In fact, when excess in the fibroblast content of tumor stroma reaches the desired level, the stroma will tend to act as a suppressor of the tumor (Mortezaee, 2021a).…”

Section: Cells and Signaling Of The Tme And The Characteristics Of An Abnormal Stromal Bed In A Tumormentioning

confidence: 99%

Normalization in tumor ecosystem: Opportunities and challenges

Mortezaee

2021

Cell Biology International

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Current research in cancer therapy aims to exploit efficient strategies to have long‐lasting effects on tumors and to reduce or even revoke the chance of recurrence. Within the tumor stroma, O2 and nutrients are abnormally distributed between various cells (preferentially for supplying cancer cells), the immune contexture is abnormally positioned (permissive essentially for cells exhibiting tumor‐promoting capacity), the fibroblast and fibrotic content is abnormally distributed (presence of both extracellular matrix [ECM] stiffening and ECM‐degrading factors both for tumor‐promoting purposes), and the tumor vasculature is abnormally orchestrated (for hindering drug delivery and increasing the chance of tumor metastasis). Resistance is actually an adaptive response to an imbalance in the tumor ecosystem; thus, the key consideration for effective cancer therapy is to bring back the normal status in this ecosystem so as to reach the desired durable outcome. Vascular normalization, metabolic modulation (glucose delivery in particular), balancing cellular dispersion, and balancing the pH rate and O2 delivery within the tumor microenvironment are suggested strategies to reverse abnormality within the tumor stroma.

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Enriched cancer stem cells, dense stroma, and cold immunity: Interrelated events in pancreatic cancer

Cited by 75 publications

References 60 publications

The current knowledge concerning solid cancer and therapy

The current knowledge concerning solid cancer and therapy

Tissue Multiplex Analyte Detection in Anatomic Pathology – Pathways to Clinical Implementation

Normalization in tumor ecosystem: Opportunities and challenges

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