Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster session 13

1166P - Multi-modal and longitudinal characterization of the tumor and immune microenvironment from primary melanoma to in-transit and distant metastasis

Date

21 Oct 2023

Session

Poster session 13

Topics

Translational Research

Tumour Site

Melanoma

Presenters

Giuseppe Tarantino

Citation

Annals of Oncology (2023) 34 (suppl_2): S651-S700. 10.1016/S0923-7534(23)01941-5

Authors

G. Tarantino1, A. Zaremba2, T. Vallius3, F. Rambow4, L. Zimmer2, A. Sucker5, E. Livingstone6, R. Pelletier7, S. MAKHZAMI4, G. Murphy8, C. Lian8, P. Sorger7, D. Liu1, D. Schadendorf9

Author affiliations

  • 1 Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 02215 - Boston/US
  • 2 Dermatology, Universitätsklinikum Essen, 45147 - Essen/DE
  • 3 Department Of Oncology, Turku University Hospital (Tyks), Boston/US
  • 4 Applied Computational Cancer Research, University Hospital Essen, Essen/DE
  • 5 Dermatology, University Hospital Essen, Essen/DE
  • 6 Dermatology Department, University Hospital Essen Westdeutsches Tumorzentrum, 45147 - Essen/DE
  • 7 Laboratory Of Systems Pharmacology, Harvard Medical School, 2115 - Boston/US
  • 8 Dermatology, Brigham and Women's Hospital, 2115 - Boston/US
  • 9 Department Of Dermatology - Hautklinik, University Hospital Essen Westdeutsches Tumorzentrum, 45147 - Essen/DE

Resources

Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

Abstract 1166P

Background

In-transit metastases (ITM) in melanoma represent a clinical entity where tumor lesions are found between the primary tumor and the draining lymph node. ITM is associated with worse prognosis. However, a significant subset of patients have discordance with high burden of locoregional relapses, but durable distant progression free survival. We studied two such patients to profile the dynamics and evolution of longitudinal tumor samples and identify mechanisms underlying these heterogeneous phenotypes.

Methods

We used whole exome sequencing (WES), bulk RNAseq, snRNAseq, and high-plex Cyclic Immunofluorescence (CyCIF) imaging to profile 28 biopsies over 7 years from pt1 (acral lentiginous melanoma, with progressive disease) and 22 biopsies over 11 years from pt2 (cutaneous melanoma, with durable remission).

Results

Pt1 (progressive disease) tumors had low to absent levels of immune infiltrate, low tumor mutational burden (TMB) and 5-hmC loss. Phylogenetic analysis revealed co-evolution of seven genetic lineages with multiple independent resistance-associated alterations; the majority of distant metastases emerged from a single lineage characterized by high aneuploidy and TMB, and a likely pathogenic missense mutation in TET2. The brain metastasis diverging early in molecular evolution but emerging late in disease had the highest TMB and aneuploidy. In another lineage, we identified WNT-beta catenin transcriptional signature contributing to TIL exclusion. In contrast, phylogenetic analysis of pt2 (durable remission) revealed six co-evolved genetic lineages with acquisition of mutational signature 11 and high TMB (53 mut/MB) after dacarbazine chemotherapy. In line with this, several tumor samples contained abundant Ki67+ CD8+ TILs and regression-like stromal changes, reflective of an autonomous effective host-immune response leading to a complete remission independent of any systemic therapy.

Conclusions

This study identifies genomic and phenotypic features linked to aggressive phenotypes and distant metastasis, including high aneuploidy, TET2 mutation, and 5hmC loss. Additional spatial analysis (GeoMx) is currently ongoing.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Doris Duke foundation.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.