Predicting tumour response to anti-PD-1 immunotherapy with computational modelling.

Predicting tumour response to anti-PD-1 immunotherapy with computational modelling. Phys Med Biol. 2018 Dec 18;: Authors: Valentinuzzi D, Simoncic U, Ursic K, Vrankar M, Turk M, Jeraj R Abstract Cancer immunotherapy is a rapidly developing field, with numerous drugs and therapy combinations waiting to be tested in pre-clinical and clinical settings. However, the costly and time-consuming trial-and-error approach to development of new treatment paradigms creates a research bottleneck, motivating the development of complementary approaches. Computational modelling is a compelling candidate for this task, however, difficulties associated with the validation of such models limits their use in pre-clinical and clinical settings. Here we propose a bottom-up deterministic computational model to simulate tumour response to treatment with anti-programmed-death-1 antibodies (anti-PD-1). The model was built with validation in mind, and so contains minimum number of parameters, and only 4 free parameters. Moreover, all model parameters can be measured experimentally. Free parameters were tuned by fitting the model to experimental data from the literature, using B16-F10 murine melanoma implanted into wild type (C57BL/6), as well as into immunodeficient (NSG) mice strains, and treated with anti-PD-1 antibodies. The model's predictive ability was verified on two independent datasets from literature with different but well-known inputs. To identify possible biomarkers o...
Source: Physics in Medicine and Biology - Category: Physics Authors: Tags: Phys Med Biol Source Type: research

Related Links:

We present a 48-year-old woman affected by metastatic uveal melanoma treated with nivolumab (3 mg/kg every 2 weeks). The patient had no previous history of autoimmune disease or dermatologic conditions. At the fourth month of treatment, on cutaneous examination, she presented multiple whitish vitiligo-like patches on the trunk, axillae, hands and face. Diagnosis of melanoma-associated leukoderma vitiliginous reaction was made. Over the following months, the melanoma-associated leukoderma lesions slowly progressed with cigarette paper-like appearance and indurated texture. A skin biopsy leaded the diagnosis of extragenital ...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Case Reports Source Type: research
ConclusionsOur cohort demonstrated an increased incidence of hypophysitis with anti ‐PD1/anti‐PDL1 in contrast to the rarity of primary thyroid dysfunction with anti‐CTLA4 treatment. These results could be attributed to genetic/ethnic differences. Sequential treatment is, for the first time to our knowledge, reported to increase the risk of developing hypophysitis to a level as high as that of combination therapy.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
CONCLUSION: A transcriptomic signature of primary melanoma was identified with prognostic value, including in stage I melanoma and in patients undergoing immunotherapy. PMID: 31515461 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
CONCLUSIONS: The combination of TMB and CNA can jointly stratify multiple metastatic tumors into groups with different prognosis and heterogenous clinical responses to ICI treatment. Patients with TMBhighCNAlow cancer can be an optimal subgroup for ICI therapy. PMID: 31515453 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
ConclusionsImmunosuppression resulted in clinical remission of each irAE, highlighting the importance of vigilance for autoimmune complications in patients treated with checkpoint inhibition, even after immunotherapy cessation.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Publication date: 10 September 2019Source: Cell Reports, Volume 28, Issue 11Author(s): Andrew J. Freeman, Stephin J. Vervoort, Kelly M. Ramsbottom, Madison J. Kelly, Jessica Michie, Lizzy Pijpers, Ricky W. Johnstone, Conor J. Kearney, Jane OliaroSummaryDespite the clinical success of cancer immunotherapies, the majority of patients fail to respond or develop resistance through disruption of pathways that promote neo-antigen presentation on MHC I molecules. Here, we conducted a series of unbiased, genome-wide CRISPR/Cas9 screens to identify genes that limit natural killer (NK) cell anti-tumor activity. We identified that ge...
Source: Cell Reports - Category: Cytology Source Type: research
Immune checkpoint inhibition and in particular anti-PD-1 immunotherapy have revolutionized the treatment of advanced melanoma. In this regard, higher tumoral PD-L1 protein (gene name: CD274) expression is associa...
Source: Journal of Experimental and Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Research Source Type: research
CONCLUSIONS: While having only a small impact on basal PD-L1 expression, both wildtype and mutated p53 play an important positive role for IFN-ɣ-induced PD-L1 expression in melanoma cells by supporting JAK2 expression. Future studies should address, whether p53 expression levels might influence response to anti-PD-1 immunotherapy. PMID: 31506076 [PubMed - in process]
Source: Clin Med Res - Category: Research Authors: Tags: J Exp Clin Cancer Res Source Type: research
ConclusionsPD-1 inhibitors are now widely used in a multitude of cancer types including melanoma, advanced non-small cell lung cancer, metastatic renal cell carcinoma, and Hodgkin lymphoma amongst others. While these agents are often well tolerated, they are associated with a unique profile of immune-related toxicities that can cause significant morbidity and mortality. Education of both patients and healthcare providers is essential for diagnosis and treatment of these adverse events early in their course. This case highlights the uncommon but potentially serious PD-1-associated toxicity of myopathy and rhabdomyolysis alo...
Source: Experimental Hematology and Oncology - Category: Cancer & Oncology Source Type: research
AbstractImmunotherapy with checkpoint inhibitors revolutionized melanoma treatment in both the adjuvant and metastatic setting, yet not all metastatic patients respond, and metastatic disease still often recurs among immunotherapy-treated patients with locally advanced disease. TNFSF4 is a co-stimulatory checkpoint protein expressed by several types of immune and non-immune cells, and was shown in the past to enhance the anti-neoplastic activity of T cells. Here, we assessed its expression in melanoma and its association with outcome in locally advanced and metastatic disease. We used publicly available data from The Cance...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
More News: Biology | Cancer | Cancer & Oncology | Immunotherapy | Melanoma | Physics | Skin Cancer | Study