Abstract 1132P
Background
Uveal melanoma (UM) is a rare form of melanoma having poor responses to currently available systemic agents. Our goal is to understand differences in chemokine expression in relation to tumor genetics and response to immunotherapy.
Methods
UM patient tumors (N=278, 41 primary, 174 liver mets and 63 other mets) were profiled by NGS DNA/RNA at Caris Life Sciences (Phoenix, AZ). Chemokine expression, high/Low (H/L) defined as samples with >75th- or <25th-percentile of transcripts per million (TPM). Tumor microenvironment (TME) cell fraction estimated by RNA, with median fold changes (H/L) or proportion of samples with non-zero fraction reported (Table). PDL1+ (SP142) tested by IHC. Survival data obtained from insurance claims.
Results
Primary tumors had increased expression of CXCR4, CXCR1, CXCR2, CCL27 and CXCL13 compared to liver mets (FC range 1.2-4.2), while CXCL2 expression was increased in liver mets (2.3, p<0.01). In liver mets, increased infiltration of immunosuppressive cells was observed for CXCR4-H and CXCL12-H tumors(Table). Only M1 macrophages, CD8+ T cells and B cells were increased for CXCR4-H and CXCL12-H primary tumors. PDL1+ rates were increased in CXCR4-H tumors overall (H 36% vs L 13%, p<0.05). In liver mets, SF3B1 mutation was associated with lower CXCL1 and CXCL2 expression compared to WT (0.35- and 0.47-fold, respectively, p-<0.01). BAP1-mutated liver mets showed increased CXCL1 expression (2.0-fold, p-0.04), whereas CCR10 expression was increased in BAP1-mutated primary tumors (2.6-fold, p-0.02). Among immunotherapy treated patients with liver mets, there was a trend for improved survival for CXCL12 H (n=13) vs L (n=12) (HR 0.51 (0.21-1.3), p=0.14) and CXCR4 H (n=13) vs L (n=12) (HR 0.49 (0.20-1.2), p=0.12) though not significant. Table: 1132P
TME (liver mets): CXCR4/CXCL12 median fold change (H/L) (where median is 0, % non-zero H vs L).
| Immune Cell | CXCR4 Median FC (H/L) or non-zero% | p-value | CXCL12 Median FC (H/L) or non-zero% | p-value |
| Monocyte | 13% vs 0% | 0.01 | 37% vs 11% | 0.31 |
| Treg | 2.9 | <0.01 | 2.9 | <0.01 |
| T cell CD8 | 70% vs 28% | <0.01 | 67% vs 34% | <0.01 |
| T cell CD4 | 32% vs 13% | 0.02 | 37% vs 11% | 0.01 |
| NK cell | 1.4 | <0.001 | 1.5 | <0.001 |
| Macrophage M2 | 1.3 | 0.002 | 1.3 | <0.001 |
| Macrophage M1 | 92% vs 50% | <0.01 | 96% vs 49% | <0.001 |
| B cell | 1.6 | <0.01 | 1.3 | 0.02 |
Conclusions
Our results suggest chemokines are differentially expressed in tumors harboring the common alterations associated with medium risk of distant metastases.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Caris Life Sciences.
Disclosure
Y. Baca, A. Elliott, P. Walker, F. Abdulla: Financial Interests, Institutional, Financially compensated role: Caris Life Sciences. All other authors have declared no conflicts of interest.
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