Tumor endothelial cells as a potential target of metronomic chemotherapy

Kim, Ji Yoon; Kim, Young‐Myeong

doi:10.1007/s12272-018-01102-z

Cited by 34 publications

(41 citation statements)

References 89 publications

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“…The conflict between cancer and the immune system has long been established [1]. Immunotherapies are being investigated to augment the anti-tumor effects of the immune system and promote long-term cancer control [2]. CD8 + cytotoxic T cells (CTLs) are the main players driving the adaptive immune response against cancer and execute tumor-specific immune responses, rendering them the primary endpoint to most immunotherapies [3,4].…”

Section: Introductionmentioning

confidence: 99%

The Evolving Role of CD8+CD28− Immunosenescent T Cells in Cancer Immunology

Huff

Kwon

Henriquez

et al. 2019

IJMS

132

118

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Functional, tumor-specific CD8+ cytotoxic T lymphocytes drive the adaptive immune response to cancer. Thus, induction of their activity is the ultimate aim of all immunotherapies. Success of anti-tumor immunotherapy is precluded by marked immunosuppression in the tumor microenvironment (TME) leading to CD8+ effector T cell dysfunction. Among the many facets of CD8+ T cell dysfunction that have been recognized—tolerance, anergy, exhaustion, and senescence—CD8+ T cell senescence is incompletely understood. Naïve CD8+ T cells require three essential signals for activation, differentiation, and survival through T-cell receptor, costimulatory receptors, and cytokine receptors. Downregulation of costimulatory molecule CD28 is a hallmark of senescent T cells and increased CD8+CD28− senescent populations with heterogeneous roles have been observed in multiple solid and hematogenous tumors. T cell senescence can be induced by several factors including aging, telomere damage, tumor-associated stress, and regulatory T (Treg) cells. Tumor-induced T cell senescence is yet another mechanism that enables tumor cell resistance to immunotherapy. In this paper, we provide a comprehensive overview of CD8+CD28− senescent T cell population, their origin, their function in immunology and pathologic conditions, including TME and their implication for immunotherapy. Further characterization and investigation into this subset of CD8+ T cells could improve the efficacy of future anti-tumor immunotherapy.

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Section: Introductionmentioning

confidence: 99%

The Evolving Role of CD8+CD28− Immunosenescent T Cells in Cancer Immunology

Huff

Kwon

Henriquez

et al. 2019

IJMS

132

118

View full text Add to dashboard Cite

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“…Analysis of the phenomenon of radiation hormesis showed that it does not disprove a linear hypothesis, being a result of redirection of morphogenic potency of the host from cancer tissue' growth to reparation/regeneration of the multitude of sub-lethal injures in non-malignant tissues of the body [71]. Giving low doses of cytotoxic chemotherapy may act that indirect way, simulating direct inactivation of cancer cells due to insufficiency of tumor endothelial net renewal [72]. We support the actu-…”

Section: Resultsmentioning

confidence: 52%

Cancer Uses the Common Morphogenesis Source of the Host

Shoutko¹

2020

OJBIPHY

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Trophic properties of hematopoietic stem cells can influence the malignant growth alternatively to immune control. The annual growth of the body mass by age in adult populations of welfare countries used as the most common criterion of metabolic and proliferative tissue activity, and these data compared with death' rate for malignant and somatic diseases in different age-groups of the same countries. The rate of physiologic involution of different cell populations in the lymphoid lineage by age also involved in correlations between the above parameters. A decrease in death rate for cancer and increase it's for non-malignant diseases found in 60+ populations, which have the lowest physiological temp of renewal of lymphocytes number and mass of the body. The lack of both the thymus gland volume and proliferative activity of naive lymphocytes reduces physiological body mass renewal as well as the cancer death rate but enhances somatic death rate, opposing to anticancer immunity at large. A protumor character of the lymphopoietic system's relation with malignancy seems more realistic than defending one.

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“…Metronomic chemotherapy, based on the continuous administration of low-dose cytotoxic agents without extended intervals, is an emerging potential method of reducing side effects of high-dose bolus treatments in various settings for cancer treatment [265,266]. More interestingly, several cytotoxic drugs have anti-angiogenic properties if administered frequently and at lower doses compared with standard schedules containing maximal tolerated doses (MTD).…”

Section: Future Perspectives—possible Answers To Therapy Resistancementioning

confidence: 99%

“…Thus, slowly proliferating tumors might be kept in a dormant, non-metastatic state. Although the exact mechanisms are not known, a reduction of VEGF expression has been observed [266,267,268]. In addition, metronomic regimes might also be efficient against advanced metastatic disease when combined with explicit angiogenesis inhibitors; e.g., bevacizumab [269,270,271,272].…”

Section: Future Perspectives—possible Answers To Therapy Resistancementioning

confidence: 99%

Trends and Challenges in Tumor Anti-Angiogenic Therapies

Jászai

Schmidt

2019

Cells

171

118

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Excessive abnormal angiogenesis plays a pivotal role in tumor progression and is a hallmark of solid tumors. This process is driven by an imbalance between pro- and anti-angiogenic factors dominated by the tissue hypoxia-triggered overproduction of vascular endothelial growth factor (VEGF). VEGF-mediated signaling has quickly become one of the most promising anti-angiogenic therapeutic targets in oncology. Nevertheless, the clinical efficacy of this approach is severely limited in certain tumor types or shows only transient efficacy in patients. Acquired or intrinsic therapy resistance associated with anti-VEGF monotherapeutic approaches indicates the necessity of a paradigm change when targeting neoangiogenesis in solid tumors. In this context, the elaboration of the conceptual framework of “vessel normalization” might be a promising approach to increase the efficacy of anti-angiogenic therapies and the survival rates of patients. Indeed, the promotion of vessel maturation instead of regressing tumors by vaso-obliteration could result in reduced tumor hypoxia and improved drug delivery. The implementation of such anti-angiogenic strategies, however, faces several pitfalls due to the potential involvement of multiple pro-angiogenic factors and modulatory effects of the innate and adaptive immune system. Thus, effective treatments bypassing relapses associated with anti-VEGF monotherapies or breaking the intrinsic therapy resistance of solid tumors might use combination therapies or agents with a multimodal mode of action. This review enumerates some of the current approaches and possible future directions of treating solid tumors by targeting neovascularization.

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Tumor endothelial cells as a potential target of metronomic chemotherapy

Cited by 34 publications

References 89 publications

The Evolving Role of CD8+CD28− Immunosenescent T Cells in Cancer Immunology

The Evolving Role of CD8+CD28− Immunosenescent T Cells in Cancer Immunology

Cancer Uses the Common Morphogenesis Source of the Host

Trends and Challenges in Tumor Anti-Angiogenic Therapies

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