Sequential immune monitoring in patients with melanoma and renal cell carcinoma treated with high-dose interleukin-2: immune patterns and correlation with outcome

Abstract Interleukin-2 (IL-2) therapy leads to clinically relevant responses in 10–16 % of patients with metastatic melanoma (MMEL) or 10–30 % of patients with metastatic renal cell carcinoma (MRCC). To date, no biomarkers have been validated to identify patients who are likely to respond. We hypothesized that changes in T cell subset distribution in patients undergoing IL-2 therapy may correlate with treatment outcomes. Immune profiles of 64 patients (27-MMEL, 37-MRCC) were evaluated using flow cytometry at baseline, during (≥three doses) and at the end of treatment cycle (30 ± 6 h after last dose), through two courses of IL-2 therapy. Changes in distribution and phenotype of circulating CD4 and CD8 lymphocyte subsets were compared (1) based on cancer types and (2) intra-patient during the course of the IL-2 therapy. Exploratory analysis of immunologic profiles was also performed based on treatment outcome. Independent of cancer type, IL-2 led to a transient decrease of circulating effector lymphocytes, while regulatory T cells gradually increased. Interleukin-2 differentially affected a subset of CD8 T cell expressing Foxp3, depending on malignancy type. In MMEL patients, IL-2 gradually expanded circulating CD8 Foxp3+ cells; in MRCC patients, IL-2 transiently increased expression of CD103 and CCR4 homing markers. Monitoring of adaptive immune variables early on and during the course of IL-2 therapy revealed transient a...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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In this study, we describe the path to identification of BAP1-TPDS in 21 probands found in the Netherlands and the family history at the time of presentation. We report two cases of de novo BAP1 germline mutations (2/21, 9.5%). Findings of this study combined with previously published literature, led to a proposal of guidelines for genetic referral. We recommend genetic analysis in patients with ≥2 BAP1-TPDS-associated tumors in their medical history and/or family history. We also propose to test germline BAP1 in patients diagnosed with UM <40 years, CM <18 years, MMe <50 years, or RCC <4...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
Interview with Suzanne L. Topalian, author of Five-Year Survival and Correlates Among Patients With Advanced Melanoma, Renal Cell Carcinoma, or Non–Small Cell Lung Cancer Treated With Nivolumab
Source: JAMA Specialty Journals Author Interviews - Category: General Medicine Source Type: podcasts
(Johns Hopkins Medicine) A research team led by experts at the Bloomberg~Kimmel Institute for Cancer Immunotherapy at the Johns Hopkins Kimmel Cancer Center reports favorable five-year survival rates from the first multidose clinical trial of the immunotherapy drug nivolumab (anti-PD-1) as a treatment for patients whose previous therapies failed to stem their advanced melanoma, renal cell carcinoma (RCC) or non-small-cell lung cancer (NSCLC).
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Authors: Zhang C, Li H, Wang J, Zhang J, Hou X Abstract Malignant melanoma (MM) is the most aggressive form of skin cancer originating from melanocytes with increased proliferative and metastatic ability. Previous studies have revealed that microRNA-338-3p (miR-338-3p) functions as a tumor suppressor in several types of cancer, including cervical cancer, renal cell carcinoma and thyroid cancer. However, the function and mechanism underlying the action of miR-383-3p in MM remain unclear. In the study, aberrant downregulation of miR-338-3p was observed in 60 pairs of MM and adjacent non-tumor tissue using quantitativ...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Publication date: Available online 11 July 2019Source: American Journal of Kidney DiseasesAuthor(s): Roman Shingarev, Ilya G. GlezermanImmunologic control of malignancy has long been recognized as an important determinant of disease progression. Recent advances in immunology have led to the focus on several mechanisms that can be targeted to achieve tumor suppression. In particular, checkpoint inhibition has evolved in less than a decade to become one of the most important strategies in cancer therapy, with a meaningful improvement in patient survival. Six agents have been approved for clinical use to date and many more ar...
Source: American Journal of Kidney Diseases - Category: Urology & Nephrology Source Type: research
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Source: Radiotherapy and Oncology : journal of the European Society for Therapeutic Radiology and Oncology - Category: Radiology Authors: Tags: Radiother Oncol Source Type: research
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Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
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Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: REVIEW Source Type: research
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Source: Gastrointestinal Endoscopy - Category: Gastroenterology Authors: Tags: Tuesday abstract Source Type: research
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