• antihormonal therapy
• breast cancer
• estrogen receptor
• human epidermal growth factor receptor 2 (HER2)
• immunotherapy
• metronomic chemotherapy
• progesterone receptor
• sentinel lymph node biopsy
• targeted therapy
• trastuzumab

• Apoptosis
• Cachectic muscle loss
• Chemotherapeutic agents
• Oxidative stress
• Protein metabolic imbalance
• Z526

• Animals
• Cachexia/drug therapy
• Cachexia/pathology
• Cachexia/chemically induced
• Cachexia/metabolism
• Oxidative Stress/drug effects
• Apoptosis/drug effects
• Mice
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/adverse effects
• Muscular Atrophy/drug therapy
• Muscular Atrophy/chemically induced
• Muscular Atrophy/metabolism
• Muscular Atrophy/pathology
• Male
• Signal Transduction/drug effects
• TOR Serine-Threonine Kinases/metabolism
• NF-kappa B/metabolism
• Muscle Fibers, Skeletal/drug effects
• Muscle Fibers, Skeletal/metabolism
• Muscle Fibers, Skeletal/pathology
• Cell Line, Tumor
• STAT3 Transcription Factor/metabolism
• Proto-Oncogene Proteins c-akt/metabolism
• Mice, Inbred BALB C
• Cell Line
• Muscle Proteins/metabolism
• Muscle, Skeletal/drug effects
• Muscle, Skeletal/metabolism
• Muscle, Skeletal/pathology

• Antigen presenting cells. stem-like T cells
• Checkpoint inhibitors
• Metronomic chemotherapy

• Humans
• Antineoplastic Combined Chemotherapy Protocols/pharmacology
• T-Lymphocytes
• Neoplasms/drug therapy
• Administration, Metronomic
• Antigen-Presenting Cells

• Colorectal cancer
• Combination
• Immune checkpoint inhibitor
• Low dose chemotherapy

• Oral cavity
• apoptosis
• arachidonic acid
• chemotherapy
• head and neck cancers
• nucleic acid
• oral cancer
• squamous cell carcinoma

• Aromatase inhibitor
• Metastatic breast cancer
• Oral vinorelbine
• Randomized phase II

• Humans
• Aged
• Female
• Vinorelbine/therapeutic use
• Breast Neoplasms/pathology
• Aromatase Inhibitors/therapeutic use
• Antineoplastic Combined Chemotherapy Protocols/adverse effects
• Vinblastine/adverse effects
• Neoplasm Metastasis
• Treatment Outcome

• Les Laboratories Pierre Fabre

• anticancer
• bleomycin
• electrochemotherapy
• electroporation
• humoral and cellular immunity
• immunology
• immunomodulation
• in vivo
• nanosecond
• pulsed electric fields

Tregs are able of suppressing tumor-specific effector cells, such as lymphocytes CD8+, CD4+ and Natural Killer cells. Different drugs, especially different schedules of administration, like metronomic chemotherapy (mCHT), seem to be able to increase anticancer immunity, by acting on downregulation of Tregs. Most of the data available regarding the immunomodulating effect of mCHT have been obtained with Cyclophosphamide (CTX). Aim of the present study was to explore the effects of mVRL and mCAPE administration, alone or in combination, on T cells. Observation of 13 metastatic breast cancer patients lasted controlling for 56 days, where Treg frequencies and function, spontaneous anti-tumor T-cell responses were monitored, as well as the clinical outcome. No depletion in Treg absolute numbers, or percentage of T lymphocytes, was observed. Only in 5 patients, a modest and transient depletion of Tregs was observed during the first 14 days of treatment. To better describe the effect on Tregs, we subsequently looked at the variations in Memory, Naïve and Activated Treg subpopulations: we observed a trend in reduction for memory Treg (Treg MEM) and an increase for Treg Naïve (Treg NAIVE) and Treg Activated (Treg ACT) components. We finally analyzed the average trend of Treg in the Treg depleted patients and non-depleted ones, without fiding any significant differences. The trend of the Treg MEM appeared different, showing a reduction during the first 14 days, followed by an increase at the levels before treatment at Day 56 in the group of depleted patients and a progressive substantial reduction in the group of non-depleted patients along the entire course of treatment. Opposed to the data known, treatment with mVRL w/o mCAPE did not show any effect on Tregs.

• Breast Cancer
• Metronomic chemotherapy
• Treg
• Vinorelbine

• combination
• drug therapy
• immunotherapy
• lymphocytes
• tumor escape
• tumor-infiltrating

• Glioblastoma
• Temozolomide
• established cell lines
• limitations of experimental systems

• Tregs
• anti-CTLA-4 immunotherapy
• immunosuppression
• photothermal therapy
• tumor microenvironment

• Animals
• Breast Neoplasms/immunology
• Breast Neoplasms/pathology
• Breast Neoplasms/therapy
• CD8-Positive T-Lymphocytes/drug effects
• CTLA-4 Antigen/antagonists & inhibitors
• CTLA-4 Antigen/immunology
• Combined Modality Therapy
• Disease Models, Animal
• Female
• Ferric Compounds/chemistry
• Ferric Compounds/pharmacology
• Humans
• Hyperthermia, Induced/methods
• Immune Tolerance/drug effects
• Immune Tolerance/immunology
• Immunotherapy
• Mice
• Nanoparticles/chemistry
• Phototherapy
• T-Lymphocytes, Regulatory/immunology
• Tumor Microenvironment/drug effects

• P30 CA046592 NCI NIH HHS

• Hypoxia
• Immune checkpoint molecule
• Myeloid-derived suppressor cell
• Regulatory T cell
• Tumor microenvironment
• Tumor-associated macrophage
• VEGF

• Cancer
• Cytotoxic T lymphocytes (CTLs)
• Immune system
• Melatonin
• Mitochondria
• Natural killer (NK) cells
• T regulatory cells (tregs)
• Tumor microenvironment (TME)

• chemotherapy
• cytotoxic drugs
• dogs
• dose-intense
• metronomic
• review

• Angiogenesis
• Antitumor immunity
• Endothelial cell
• Immunosuppression
• Metronomic chemotherapy

Despite recent advances in early detection and improvements in chemotherapy for colon cancer, the patients still face poor prognosis of postoperative recurrence and metastasis, the median survival for patients with metastatic colorectal cancer is approximately 22–24 months. Some immunotherapeutic approaches had been attempted in colon cancer patients to significantly increase overall survival. A vaccine based approach has shown a novel direction for colon cancer prevention and therapy.

In this study, the experiments were designed including prevention and therapeutic stages in order to attain effect against tumor recurrence in clinical settings. The anti-tumor efficacy of a novel cytokine adjuvant vaccine that contained cytokines GM-CSF and IL-2 and inactivated colon CT26.WT whole cell antigen was evaluated in BALB/c mouse tumor models by measuring tumor growth post vaccination and the survival time of tumor-bearing mice, analyzing the expression and distribution of CD4, CD8, CD11c, CD80, CD86 and CD83 positive cells in control and treated mice by flow cytometry and immunochemistry. The tumor-specific cytotoxic T cells (CTL) were analyzed by tumor proliferation and the lactic dehydrogenates (LDH) release assays. IFN-γ, IL-2 and GM-CSF secretion in serum was assayed by ELISA.

Our results suggested that cytokine adjuvant vaccine significantly inhibited tumor growth and extended the survival period at least 160d. It was found that the levels of CD8 + T and the tumor-specific cytotoxicity were significantly higher in prevention and treatment group vaccinated by cytokine adjuvant vaccine. CD8 + T cells play a key role in anti-tumor response.

The novel GM-CSF and IL-2 based adjuvant vaccine effectively activated autologous T-cell response and represented a promising immunotherapeutic approach for patients with colon cancer.

The online version of this article (doi:10.1186/s12865-016-0172-x) contains supplementary material, which is available to authorized users.

• CT26.WT
• Colon cancer
• Cytokine adjuvant
• Immunotherapy
• Tumor vaccine

• NSCLC
• breast cancer
• metronomic chemotherapy
• vinorelbine

There has, in recent years, been a paradigm shift in our understanding of the role of the immune system in the development of cancers. Immune dysregulation, manifesting as chronic inflammation, not only facilitates the growth and spread of tumors but prevents the host from mounting effective immune defenses against it. Many attempts are being made to develop novel immunotherapeutic strategies, but there is growing evidence that a radical reevaluation of the mode of action of chemotherapeutic agents and ionizing radiation is required in the light of advances in immunology.

Based on the concept of hormesis – defined as the presence of different modes of action of therapeutic modalities at different doses – a ‘repositioning’ of chemotherapy and radiotherapy may be required in all aspects of cancer management. In the case of chemotherapy, this may involve a change from the maximum tolerated dose concept to low dose intermittent (‘metronomic’) therapy, whilst in radiation therapy, highly accurate stereotactic targeting enables ablative, antigen-releasing (immunogenic) doses of radiation to be delivered to the tumor with sparing of surrounding normal tissues. Coupled with emerging immunotherapeutic procedures, the future of cancer treatment may well lie in repositioned chemotherapy, radiotherapy, and more localized debulking surgery.

• cyberknife
• drug repositioning
• hormesis
• immunotherapy
• inflammation
• low dose metronomic chemotherapy
• mtor
• stereotactic ablative radiotherapy (sabr)
• stereotactic body radiation therapy

Secondary lymphoid tissue chemokine (SLC/CCL21), one of the CC chemokines, exerts potent antitumor immunity by co-localizing T cells and dendritic cells at the tumor site and is currently tested against human solid tumors. Here, we investigated whether the combination of recombinant adenovirus encoding murine CCL21 (Ad-mCCL21) with low-dose paclitaxel would improve therapeutic efficacy against murine cancer. Immunocompetent mice bearing B16-F10 melanoma or 4T1 breast carcinoma were treated with either Ad-mCCL21, paclitaxel, or both agents together. Our results showed that Ad-mCCL21 + low-dose paclitaxel more effectively reduced the growth of tumors as compared with either treatment alone and significantly prolonged survival time of the tumor-bearing animals. These antitumor effects of the combined therapy were linked to altered cytokine network at the tumor site, enhanced apoptosis of tumor cells, and decreased formation of new vessels in tumors. Importantly, the combined therapy elicited a strong therapeutic antitumor immunity, which could be partly abrogated by the depletion of CD4⁺ or CD8⁺ T lymphocytes. Collectively, these preclinical evaluations may provide a combined strategy for antitumor immunity and should be considered for testing in clinical trials.

• Angiogenesis
• CCL21
• cytotoxic T lymphocytes
• immunotherapy
• paclitaxel

Chemotherapy given in a metronomic manner can be administered with less adverse effects which are common with conventional schedules such as myelotoxicity and gastrointestinal toxicity and thus may be appropriate for older patients and patients with decreased performance status. Efficacy has been observed in several settings. An opportunity to improve the efficacy of metronomic schedules without significantly increasing toxicity presents with the addition of anti-angiogenic targeted treatments. These combinations rational stems from the understanding of the importance of angiogenesis in the mechanism of action of metronomic chemotherapy which may be augmented by specific targeting of the vascular endothelial growth factor (VEGF) pathway by antibodies or small tyrosine kinase inhibitors. Combinations of metronomic chemotherapy schedules with VEGF pathway targeting drugs will be discussed in this paper.

• Metronomic chemotherapy
• Vascular endothelial growth factor
• Angiogenesis
• Bevacizumab
• Vascular endothelial growth factor receptor