Harnessing nanomedicine to overcome the immunosuppressive tumor microenvironment

Sun, Bo; Hyun, Hyesun; Li, Liantao; Wang, Andrew Z.

doi:10.1038/s41401-020-0424-4

Cited by 60 publications

(41 citation statements)

References 211 publications

(288 reference statements)

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“…Despite the lack of pathology in our discovery and validation datasets, the sCMRs were enriched for sites showing altered DNAm in syndromes or disorders of sex chromosomes, X-linked loci or chromatin modellers. We also found that a subset of sCMRs had altered DNAm patterns in tumor samples, an effect that may reflect chromosomal abnormalities typical of cancer cells or the microenvironment of tumors ( 86 ). Nevertheless, it remains unknown whether sCMRs underscore sex differences in disease or susceptibility to the environment.…”

Section: Discussionmentioning

confidence: 66%

OUP accepted manuscript

Gatev

Inkster

Konwar

et al. 2021

Nucleic Acids Research

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Sex is a modulator of health that has been historically overlooked in biomedical research. Recognizing this knowledge gap, funding agencies now mandate the inclusion of sex as a biological variable with the goal of stimulating efforts to illuminate the molecular underpinnings of sex biases in health and disease. DNA methylation (DNAm) is a strong molecular candidate for mediating such sex biases; however, a robust and well characterized annotation of sex differences in DNAm is yet to emerge. Beginning with a large ( n = 3795) dataset of DNAm profiles from normative adult whole blood samples, we identified, validated and characterized autosomal sex-associated co-methylated genomic regions (sCMRs). Strikingly, sCMRs showed consistent sex differences in DNAm over the life course and a subset were also consistent across cell, tissue and cancer types. sCMRs included sites with known sex differences in DNAm and links to health conditions with sex biased effects. The robustness of sCMRs enabled the generation of an autosomal DNAm-based predictor of sex with 96% accuracy. Testing this tool on blood DNAm profiles from individuals with sex chromosome aneuploidies (Klinefelter [47,XXY], Turner [45,X] and 47,XXX syndrome) revealed an intimate relationship between sex chromosomes and sex-biased autosomal DNAm.

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Section: Discussionmentioning

confidence: 66%

OUP accepted manuscript

Gatev

Inkster

Konwar

et al. 2021

Nucleic Acids Research

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“…It can be obtained by the secretion of cytokines with the following recruitment of Treg and MDSCs (myeloid-derived suppressor cells), and changes in amino-acids metabolism. Arginine, glutamine, leucine, and tryptophan are among those which are now under investigation and establishment of their function will help to better understand the biology of cancer [6][7][8]. Due to the broad role of each of the listed amino-acids, it is not possible to describe them in detail in one manuscript.…”

Section: Mechanisms Involved In Immune Evasionmentioning

confidence: 99%

Not Only Immune Escape—The Confusing Role of the TRP Metabolic Pathway in Carcinogenesis

Kwiatkowska

Hermanowicz

Przybyszewska-Podstawka

et al. 2021

Cancers

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Background: The recently discovered phenomenon that cancer cells can avoid immune response has gained scientists' interest. One of the pathways involved in this process is tryptophan (TRP) metabolism through the kynurenine pathway (KP). Individual components involved in TRP conversion seem to contribute to cancerogenesis both through a direct impact on cancer cells and the modulation of immune cell functionality. Due to this fact, this pathway may serve as a target for immunotherapy and attempts are being made to create novel compounds effective in cancer treatment. However, the results obtained from clinical trials are not satisfactory, which raises questions about the exact role of KP elements in tumorigenesis. An increasing number of experiments reveal that TRP metabolites may either be tumor promoters and suppressors and this is why further research in this field is highly needed. The aim of this study is to present KP as a modulator of cancer development through multiple mechanisms and to point to its ambiguity, which may be a reason for failures in treatment based on the inhibition of tryptophan metabolism

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“…AMD3100, an antagonist of CXCR4, blocks the signaling of CXCR4 after binding to CXCR4, although cross-reactive to other chemokine receptors as previously reported [15], and thus play an important role in inhibition of tumor growth and metastasis. Emerging evidence demonstrates that the accumulation of immunosuppressive cells in the TME greatly reduce antitumor efficacy of the treatment, making it one of the major obstacles to cancer immunotherapy [16,17]. Immune cells are involved in different periods of tumor progression.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2021

Int J Cancer Clin Res

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AMD3100 (Plerixafor), a specific antagonist of CXCR4, is the most potent small molecule non-peptide inhibitor to CXCR4/CXCL12 axis. The chemokine receptor CXCR4 and its ligand CXCL12 (SDF-1) expressed in a variety of tumor cells play an important role in regulating tumor biological behavior. The tumor microenvironment (TME) is the environment around a tumor, comprising blood vessels, immune cells, fibroblasts, signaling molecules and the extracellular matrix which are involved in tumor growth, invasion, metastasis, immune escape and tumor eradication. Although AMD3100 has been intensively investigated in tumor biology, it remains unclear how this treatment regimen modulates immune cells in the TME, which in turn affects the antitumor efficacy of other therapies. In this review, we specifically revisit the evidence from our and others' studies that AMD3100 acts as an immunomodulator to regulate immune responses in the TME and provide the perspective of synergy of AMD3100 with other therapeutics to prevent tumor development, progression, and metastasis.

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Harnessing nanomedicine to overcome the immunosuppressive tumor microenvironment

Cited by 60 publications

References 211 publications

OUP accepted manuscript

OUP accepted manuscript

Not Only Immune Escape—The Confusing Role of the TRP Metabolic Pathway in Carcinogenesis

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