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Tumor Immunotherapy

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.

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Predictive Immune-Checkpoint Blockade Classifiers Identify Tumors Responding to Inhibition of PD-1 and/or CTLA-4.

Oscar Krijgsman¹, Kristel Kemper¹, Julia Boshuizen¹

¹Department of Molecular Oncology and Immunology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research

|July 7, 2021

Summary

New melanoma biomarkers predict response to immune-checkpoint blockade (ICB) monotherapy or combination treatment. These signatures help identify patients who benefit most from anti-PD-1 or anti-CTLA-4 therapies, optimizing treatment selection.

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Published on: August 14, 2019

Area of Science:

Oncology
Immunology
Bioinformatics

Background:

Combination immune-checkpoint blockade (ICB) with anti-PD-1 and anti-CTLA-4 improves melanoma patient outcomes.
However, combination ICB is associated with severe immune-related adverse events and high costs.
Predictive biomarkers are needed to guide treatment selection between monotherapy and combination ICB.

Purpose of the Study:

To develop and validate predictive signatures for response to anti-PD-1 and anti-CTLA-4 therapies in melanoma.
To differentiate patients who benefit from monotherapy versus combination ICB.

Main Methods:

Utilized patient-derived melanoma xenografts (PDX) to isolate tumor cell-intrinsic ('InTumor') and tumor cell-extrinsic ('ExTumor') RNA signatures.
Employed the XenofilteR deconvolution algorithm to separate human tumor cell RNA from the tumor microenvironment (TME).
Correlated 'InTumor' and 'ExTumor' signatures with response to anti-PD-1 and anti-CTLA-4, respectively.

Main Results:

The 'InTumor' signature predicts response to anti-PD-1 monotherapy.
The 'ExTumor' signature predicts response to anti-CTLA-4 therapy.
Combined signatures accurately identify patients likely to benefit from combination ICB and those unlikely to gain additional benefit from adding anti-CTLA-4 to anti-PD-1.

Conclusions:

Novel 'InTumor' and 'ExTumor' signatures can distinguish melanoma patients who require combination ICB from those who benefit from monotherapy.
These biomarkers offer a potential strategy to personalize ICB treatment selection, improving efficacy and reducing toxicity and cost.