We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
Technopath Clinical Diagnostics - An LGC Company

Download Mobile App




Events

ATTENTION: Due to the COVID-19 PANDEMIC, many events are being rescheduled for a later date, converted into virtual venues, or altogether cancelled. Please check with the event organizer or website prior to planning for any forthcoming event.

New Biomarkers to Help Gauge Response of Melanoma Patients to Immune Checkpoint Therapy

By LabMedica International staff writers
Posted on 20 Sep 2022
Print article
Image: Immune checkpoint (Photo courtesy of The Wistar Institute)
Image: Immune checkpoint (Photo courtesy of The Wistar Institute)

A recent study identified biomarkers that demonstrate stable performance in predicting the response of melanoma patients to immune checkpoint inhibitor (ICI) therapy.

Since only a subset of melanoma patients respond to immunotherapy with checkpoint inhibitors, predictive biomarkers are critically needed to guide treatment decisions and develop approaches to the treatment of therapeutic resistance.

The Tumor Mutation Burden (TMB) is the only [U.S.] FDA-approved biomarker for melanoma. TMB is defined as the number of somatic mutations per megabase whereas mutational signatures are distinct mutational patterns of single base substitutions, double base substitutions, or small insertions and deletions in tumors. TMB has shown potential as a predictive biomarker with several applications, including associations reported between different TMB levels and patient response to immune checkpoint inhibitor (ICI) therapy in a variety of cancers. However, the mechanisms underlying TMB association with prolonged ICI survival are not entirely understood and may depend on numerous confounding factors.

Investigators at the The Wistar Institute (Philadelphia, PA, USA) sought to identify better ICI response biomarkers based on tumor mutations. Toward this end, they evaluated a variety of feature selection and classification methods and identified key mutated biological processes that provided improved predictive capability compared to the TMB.

Over the course of the study, the investigators worked with training and validation mutation and clinical datasets from metastatic melanoma patients treated with anti-PD1. For training, they used 144 melanoma patients’ samples, including somatic mutations and anti-PD1 response information. For validation, they used 68 melanoma patients’ samples with somatic mutations and relevant clinical data. To further test the models, they used an additional 38 anti-PD1-treated melanoma patients’ samples. For all datasets, responders were defined as patients with complete or partial response.

The top mutated processes identified by the study were involved in leukocyte and T-cell proliferation regulation. These markers demonstrated stable predictive performance across different data cohorts of melanoma patients treated with ICI. Identification of these mutated processes is expected to substantially improve prediction of response to ICI by melanoma patients over that obtainable from the TMB.

“This work aims to identify better and more biologically interpretable genomic predictors for immunotherapy responses,” said senior author Dr. Noam Auslander, assistant professor of molecular and cellular oncogenesis at the Wistar Institute. “We need better biomarkers to help select patients that are more likely to respond to ICI therapy and understand what factors can help to enhance responses and increase those numbers.”

The study was published in the September 19, 2022, online edition of the journal Nature Communications.

Related Links:
The Wistar Institute

Gold Supplier
Automated, Random Access Chemistry Analyzer
LIDA 300
New
Pipettor
Corning Step-R Repeating Pipettor
New
Sepsis Test
MM SEPSIS PANEL
New
M. Tuberculosis Indirect Test
LIAISON QuantiFERON-TB Gold Plus

Print article
SUGENTECH INC.

Channels

Clinical Chem.

view channel
Image: ELISA kit for liver-type fatty acid–binding protein (L-FABP). The level of L-FABP present in urine reflects the level of renal tubular dysfunction (Photo courtesy of Sekisui Medical Co)

Urinary Biomarkers Predict Weaning From Acute Dialysis Therapy

Acute kidney injury is associated with a higher risk of chronic kidney disease (CKD), end-stage renal disease, and long-term adverse cardiovascular effects. Critically ill patients with acute kidney injury... Read more

Microbiology

view channel
Image: Ring-form trophozoites of Plasmodium vivax in a thin blood smear (Photo courtesy of Centers for Disease Control and Prevention)

Immune Regulators Predict Severity of Plasmodium vivax Malaria

Cytokines and chemokines are immune response molecules that display diverse functions, such as inflammation and immune regulation. In Plasmodium vivax infections, the uncontrolled production of these molecules... Read more

Pathology

view channel
Image: Breast cancer spread uncovered by new molecular microscopy (Photo courtesy of Wellcome Sanger Institute)

New Molecular Microscopy Tool Uncovers Breast Cancer Spread

Breast cancer commonly starts when cells start to grow uncontrollably, often due to mutations in the cells. Overtime the tumor becomes a patchwork of cells, called cancer clones, each with different mutations.... Read more

Industry

view channel
Image: With Cell IDx’s acquisition, Leica Biosystems will be moving its multiplexing menu forward (Photo courtesy of Leica Biosystems)

Leica Biosystems Acquires Cell IDx, Expanding Offerings in Multiplexed Tissue Profiling

Leica Biosystems, a technology leader in automated staining and brightfield and fluorescent imaging (Nussloch, Germany), has acquired Cell IDx, Inc. (San Diego, CA, USA), which provides multiplex staining... Read more
Copyright © 2000-2022 Globetech Media. All rights reserved.