1169P - Tumour transcriptional and spatial protein profiling in Mexican patients reveals that acral lentiginous melanoma is characterized by an immunosuppressive microenvironment

Background

Acral lentiginous melanoma (ALM), although overall a rare type of melanoma, is the most common form of the disease in a number of countries in Latin America, Africa, and Asia; it is associated with a poor prognosis and recurrence. In this study, we seek to gain a better understanding of the tumor-immune components of ALM and their relationship to transcriptional programs.

Methods

Tumour samples were collected from patients undergoing treatment at the National Cancer Institute of Mexico, and have been annotated with vast clinical information. We performed transcriptome sequencing through exome-capture bulk RNA-sequencing on 65 primary tumors from 64 Mexican patients, and did spatial protein profiling using a tissue microarray on 110 tumor segments from 45 patients. Samples were collected at the National Cancer Institute of Mexico and have been annotated with vast clinical information.

Results

We identified differentially expressed genes such as CXCL8, MMP1, and TERT in ulcerated lesions. RNA deconvolution showed a high abundance of cancer-associated fibroblasts (CAFs) and the absence of NK cells. Consensus clustering identified three ALM subgroups based on global gene expression. Integration of spatial protein information confirmed the high abundance of CAFs- associated markers and the absence of CD56. Fibronectin, SMA, and the cancer stem cell marker CD44 were markedly elevated. We investigated expression patterns within particular regions of interest and found that fibronectin, VISTA, SMA, IDO1, CD34, CD45, CD3, HLA-DR, and CD45RO were differentially expressed in non-tumor regions, while tumor ROIs expressed B7-H3, CD127, GAPDH, and Ki-67 significantly at higher levels. Comparisons between RNA and protein for 35 targets are being conducted.

Conclusions

So far, our analyses point to genes that could drive important prognostic characteristics. We confirmed that ALM is characterized by an immunosuppressive tumor microenvironment. The role of CAFs and the mechanisms affecting NK cells require further research. The present project will enhance our understanding of the TME components and the antitumor response in an understudied disease.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Carla Daniela Robles Espinoza.

Funding

CONACyT A3-S-31603, UNAM PAPIIT IN209422, Welcome Sanger Institute International Fellowship, Melanoma Research Alliance Pilot Award #825924, William Guy Forbeck Research Foundation.

Disclosure

D. Adams: Other, Institutional, Other, DJA is supported by AstraZeneca, OpenTargets and is a paid consultant for Microbiotica: AstraZeneca. All other authors have declared no conflicts of interest.