Is your melanoma hot enough for immunotherapy?

Is your melanoma hot enough for immunotherapy?

Publication date: Apr 03, 2019

Credit: Wikipedia/CC BY-SA 3. 0 Melanomas tend to be “hot” or “cold-if they’re hot, immunotherapy lights melanoma tumors like beacons for elimination by the immune system; but 40-50 percent of melanomas are cold, making them invisible to the immune system, and patients with cold tumors tend to show little benefit from immunotherapies.

Now a University of Colorado Cancer Center study presented at the American Association for Cancer Research (AACR) Annual Meeting 2019 identifies a possible way to predict which melanomas are hot and cold: Tumors with mutations in genes leading to over-activation of the NF-kB signaling pathway were more than three times as likely to respond to anti-PD1 immunotherapy compared with tumors in which these changes were absent.

However, Amato and colleagues including William Robinson, MD, Ph. D., and first author Keith Wells, MD, show that while overall tumor mutation burden may increase the chance of important genetic changes, the immune system’s ability to see tumor tissue may depend more on specific, important changes than on overall mutation burden.

Sixty-seven percent of those responding favorably had alterations in genes associated with the NF-kB signaling pathway, compared with only 19 percent in patients whose tumors did not respond to immunotherapy.

This mutation, G34E, found only in tumors that responded to immunotherapy, has an effect like removing a limiter on NF-kB, allowing increased activation of this pathway.

“Even beyond tumor mutation burden, these specific changes could help doctors predict which melanoma patients will respond and which patients will not respond to anti-PD1 immunotherapies,” Amato says.

Concepts Keywords
AACR MS
Antigens Epithelioid sarcoma
BRAF Cancer immunotherapy
CC BY SA C-Met
Colorado Immunotherapy
Exome NF-κB
Fair Dealing Cancer
Genetic Melanoma
Immune System Proteins
Immunotherapies Medicine
Immunotherapy RTT
KB Branches of biology
Melanoma Ability tumor
Melanomas Percent tumors
Mutation Antigens surface tumor
Nucleus Total mutations tumor
Sequencing Cancers
Skin Biopsy Immunotherapy
Transcription Factor Immunotherapies
Tumor Hot cold Tumors
William Robinson Differences tumor
Hot tumor tumor
Percent melanomas
Genetic genomic tumors

Semantics

Type Source Name
gene UNIPROT TNFSF13
gene UNIPROT ANP32B
gene UNIPROT NRAS
gene UNIPROT BRAF
gene UNIPROT CD83
gene UNIPROT NFKBIE
drug DRUGBANK Tropicamide
disease MESH development
gene UNIPROT BAD
disease DOID Skin Cancer
disease MESH Skin Cancer
gene UNIPROT LAT2
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
gene UNIPROT PDCD1
gene UNIPROT SNCA
gene UNIPROT SPATA2
disease DOID Cancer
gene UNIPROT BEST1
pathway BSID Immune System
disease MESH tumors
gene UNIPROT ADHFE1

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