Abstract 2157
Background
The molecular analysis of melanoma has improved our understanding of the disease. The Cancer Genome Atlas (TCGA) Network proposed the molecular classification of melanoma in three subtypes: keratin-high, immune-high and membrane-low. However, this classification has not translated into therapeutic advances so far. Immunotherapy has contributed to improve survival, yet the mechanisms explaining differences in efficacy have not been elucidated. The aim of this study is to characterize the immune status of melanoma tumors through gene expression, and to analyze if these differences have an impact in the response to immunotherapy.
Methods
A probabilistic graphical model, followed by successive sparse k-means and consensus cluster analyses, was used to classify melanoma tumor samples from the TCGA cohort. Findings were translated into a cohort of patients treated with anti-PD1 antibodies (GSE78220, Hugo W et al) as a validation dataset.
Results
A probabilistic graphical model, including the 2,971 more variable genes from 472 melanoma samples from the TCGA dataset was built, and the resulting graph was processed to seek functional structures. Sparse k-means selected 119 genes. Gene ontology analysis showed that these genes were mainly related with immune processes. Immune genes split the population into two groups with different immune status. The so-called immune-high group included 232 patients (49%) and the immune-low group groups 238 patients (51%). The validation dataset GSE78220 provided mRNA expression in melanomas being treated with anti-PD-1 antibodies (28 biopsies belonging to 27 patients). The immune layer was translated to the new cohort by centroid method: 9 patients had immune-low tumors, whereas the remaining 18 had immune-high tumors. Kaplan Meier analysis using the clinical data from the GSE78220 cohort found a favorable response in patients with immune-low tumors (90% long-term survival).
Conclusions
We found a gene signature related to the tumor immune status that split the TCGA cohort in two groups. When applied to a cohort of patients treated with anti-PD1 antibodies, the group with immune-low tumors had 90% of long-term survival.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
2743 - The Impact of Targeted Therapies and Immunotherapy in Melanoma Brain Metastases: a Systematic Review and Meta-Analysis
Presenter: Mario Mandala
Session: Poster Display session 3
Resources:
Abstract
5479 - Intracranial Anti-Tumor Activity in Melanoma Brain Metastases with Encorafenib Plus Binimetinib: A Multicenter, Retrospective Analysis
Presenter: Jose Lutzky
Session: Poster Display session 3
Resources:
Abstract
3560 - Outcomes of Patients with Melanoma Brain Metastases (MBM) Treated with Standard of Care Therapy After Being Excluded from MBM-Specific Clinical Trials
Presenter: Kourtney Holbrook
Session: Poster Display session 3
Resources:
Abstract
3175 - The analysis of current treatment outcomes in melanoma patients with brain metastases
Presenter: Joanna Placzke
Session: Poster Display session 3
Resources:
Abstract
4550 - A multivariate model to define prognostic groups among patients with melanoma brain metastases: a 10-year retrospective cohort study
Presenter: Giacomo Pelizzari
Session: Poster Display session 3
Resources:
Abstract
4191 - The immune landscape of melanoma significantly influences survival in patients with highly mutated tumors.
Presenter: Robert Ferguson
Session: Poster Display session 3
Resources:
Abstract
1625 - Final Results from Phase II of Combination with Canerpaturev (formerly HF10), an Oncolytic Viral Immunotherapy, and Ipilimumab in Unresectable or Metastatic Melanoma in 2nd-or later line treatment
Presenter: Kenji Yokota
Session: Poster Display session 3
Resources:
Abstract
5346 - Evaluating polygenic risk score prediction model for melanoma prognosis
Presenter: Miriam Potrony
Session: Poster Display session 3
Resources:
Abstract
5477 - Impact of sarcopenia in patients with metastatic melanoma treated with immunotherapy
Presenter: Maria Grazia Vitale
Session: Poster Display session 3
Resources:
Abstract
3469 - Ancillary evaluation of systemic immune antitumor response (SIAR) and tumor growth rate (TGR) of patients (pts) with metastatic melanoma (MM) treated with radiotherapy (RT) combined with ipilimumab (ipi) in the phase 1 study Mel-Ipi-Rx.
Presenter: Celine Boutros
Session: Poster Display session 3
Resources:
Abstract