Fast-growing in-transit melanoma metastasis after intratumoral interleukin-2

Moreno‐Ramírez, D.; Alés-Martínez, Martina; Ferrándiz, Lara

doi:10.1007/s00262-014-1583-2

Cited by 3 publications

(3 citation statements)

References 3 publications

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“…Decreased activity of tumor-specific cytotoxic T can be associated with improved tumor control in vivo [ 15 ]. Enhancement of tumor growth has been observed in experimental model for cancer immunotherapy and faster tumor growth has been anecdotally observed after immunotherapy in humans [ 16 , 17 ]. In addition to classical antibody-based immunological enhancement [ 18 ], regulatory interactions between different cell types can explain such effects.…”

Section: Resultsmentioning

confidence: 99%

A Multi-Component Model of Hodgkin's Lymphoma

Staege

2015

PLoS ONE

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Hodgkin’s lymphoma is an example for a tumor with an extremely tight interaction of tumor cells with cells from the tumor micro-environment. These so-called bystander cells are not inert but interact actively with the tumor cells. Some of these cells support tumor growth by delivery of co-stimulating and anti-apoptotic signals (“helper cells”). Other cells (“killer cells”) are involved in the anti-tumor immune response which is obviously not efficient enough for tumor elimination. The activity of both helper cells and killer cells is regulated by additional cells in the stroma (“regulatory cells”). The dynamic behavior of such multi-component systems is difficult to predict. In the present paper we propose a model that can be used for simulation of essential features of this system. In this model, tumor growth depends on (i) presence of few cancer stem cells, (ii) co-stimulation of cancer cells by the tumor stroma, (iii) activity of regulatory cells that suppress killer cells without suppression of helper cells. The success of cytotoxic/cytostatic therapy in this model varies depending on the therapy-related toxicity for each of the cell populations. The model also allows the analysis of immunotherapeutic interventions. Under certain conditions, paradox enhancement of tumor growth can occur after therapeutic intervention. The model might be useful for the design of new treatment strategies for Hodgkin’s lymphoma and other tumors with prominent tumor-stroma interaction.

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Section: Resultsmentioning

confidence: 99%

A Multi-Component Model of Hodgkin's Lymphoma

Staege

2015

PLoS ONE

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“…Interleukin-2 showed efficacy in treating metastatic melanoma. However, its adverse side effects, inefficacy in large tumors, and high rates of toxicity such as allergic reactions and seizures discouraged widespread use in patients [52][53][54][55]. Interleukin-12 was also investigated as a cancer drug for its robust anti-angiogenic and immune cell-promoting activity.…”

Section: The Re-emergence Of Cancer Immunotherapymentioning

confidence: 99%

A Quantitative Systems Pharmacology Perspective on Cancer Immunology

Byrne-Hoffman

Klinke

2015

Processes

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Abstract:The return on investment within the pharmaceutical industry has exhibited an exponential decline over the last several decades. Contemporary analysis suggests that the rate-limiting step associated with the drug discovery and development process is our limited understanding of the disease pathophysiology in humans that is targeted by a drug. Similar to other industries, mechanistic modeling and simulation has been proposed as an enabling quantitative tool to help address this problem. Moreover, immunotherapies are transforming the clinical treatment of cure cancer and are becoming a major segment of the pharmaceutical research and development pipeline. As the clinical benefit of these immunotherapies seems to be limited to subset of the patient population, identifying the specific defect in the complex network of interactions associated with host immunity to a malignancy is a major challenge for expanding the clinical benefit. Understanding the interaction between malignant and immune cells is inherently a systems problem, where an engineering perspective may be helpful. The objective of this manuscript is to summarize this quantitative systems perspective, particularly with respect to developing immunotherapies for the treatment of cancer. OPEN ACCESSProcesses 2015, 3 236

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“…Interleukin-2 showed efficacy in treating metastatic melanoma. However, its adverse side effects, inefficacy in large tumors, and high rates of toxicity such as allergic reactions and seizures discouraged widespread use in patients (Heywood 1995, Karp 1996, Alexandrescu 2005, Moreno-Ramirez 2014.…”

Section: The Re-emergence Of Cancer Immunotherapymentioning

confidence: 99%

The Role of Interleukin-12 and Exosomes in the Dynamic Interplay of Cancer and the Immune System

Byrne-Hoffman¹

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THE ROLE OF INTERLEUKIN-12 AND EXOSOMES IN THE DYNAMIC INTERPLAY OF CANCER AND THE IMMUNE SYSTEM CHRISTINA NICOLE "NIKKI" BYRNE-HOFFMAN Melanoma and breast cancers account for a large number of cancer diagnoses and deaths, with 1 in 28 and 1 in 8 developing melanoma or breast cancer, respectively, in their lifetime. T Lymphocytes play a pivotal role in the immune system response to cancers and are known to evade the immune system by a variety of mechanisms, including modulation of cytokine function. A cytokine important for the function of T lymphocytes, Interleukin-12, and modulation of its Janus Kinase and activators of transcription (JAK-STAT) signaling pathway, plays a role in the immune response to tumors, especially melanoma. We examined the role of interleukin-12 receptor beta 2 as a possible target of immune system inhibition by melanoma via a cytokine sink and initiation of alternative signaling pathways to produce cell survival in melanoma, even when challenged with the cytotoxic stressor and chemotherapy drug imatinib. Additionally, exosomes, nano-sized vesicles containing immune system-inhibiting proteins and nucleic acids, have also been described as a potential mechanism of evasion. We investigated the proteomic profiles of exosomes in human breast cancers, which informed upon studies examining the nucleic acid payloads in murine melanomas against a murine cytotoxic T lymphocyte model, CTLL2 cells. We have examined the microRNA contents of exosomes from a murine B16F0 melanoma line and determined possible target cell alterations in mitochondrial respiration, DNA modification, and targeting of the Notch pathway. We concluded tumor-derived exosomes may affect the overall function of immune cells like cytotoxic T lymphocytes, and specific microRNAs and protein products contained within them may alter cell energetics and certain transcription and translation products to promote the proliferation and immune evasion abilities of melanoma, breast, and other cancers. iii DEDICATION To my son, Benjamin Scott Hoffman, I want you to know that you can do anything in life, regardless of the obstacles or the people who will try to discourage you or make you think you can't achieve your dreams. Raising you and finishing this degree in harmony has been life's biggest obstacle so far, but I know we're both the stronger for it. I am so glad you have been here to share in the joy of this chapter of my life. You have taught me the true meaning of life and love, and you and your father were my motivation when I wanted to give up. I wanted to throw in the towel, and even the whole laundry basket, but I didn't because of you. iv ACKNOWLEDGMENTS Of nearly the upmost importance, to my mentor and advisor, Dr. David Klinke, thank you for sticking it out with me and giving me a chance when others had given up on me. Your patience, mentorship, honesty, and insight helped to drive me. Your faith in my abilities gave me the final push I needed to make it this far. I know you took unfathomable risks by taking me on when I switched...

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Fast-growing in-transit melanoma metastasis after intratumoral interleukin-2

Cited by 3 publications

References 3 publications

A Multi-Component Model of Hodgkin's Lymphoma

A Multi-Component Model of Hodgkin's Lymphoma

A Quantitative Systems Pharmacology Perspective on Cancer Immunology

The Role of Interleukin-12 and Exosomes in the Dynamic Interplay of Cancer and the Immune System

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