Unveiling the tumor immune microenvironment of organ-specific melanoma metastatic sites

• DOI: 10.1136/jitc-2022-004884
• Publication Date: 2022-09-12T15:36:13Z
• Authors: Jordan W Conway; Robert V Rawson; Serigne Lo; Tasnia Ahmed; Ismael A Vergara; Tuba N Gide; Grace Heloise Att...; Matteo S Carlino; Robyn P M Saw; John F Thompson; Andrew J Spillane; Kerwin F Shannon; Brindha Shivalingam; Alexander Maxwell...; James S Wilmott; Georgina V Long; Richard A Scolyer; Ines Pires da Silva
• Keywords: Clinical/Translational Cancer Immunotherapy; Lung Neoplasms; Brain Neoplasms; Liver Neoplasms; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Lymphatic Metastasis; Tumor Microenvironment; Humans; Hepatitis A Virus Cellular Receptor 2; Melanoma; RC254-282

The liver is a known site of resistance to immunotherapy and the presence metastases associated with shorter progression-free overall survival (OS) in melanoma, while lung have been more favorable outcome. There are limited data available regarding immune microenvironment at different anatomical sites melanoma metastases. This study sought characterize compare tumor liver, brain, lung, subcutaneous (subcut) as well lymph node (LN) metastases.We analyzed OS 1924 systemic treatment-naïve patients AJCC (American Joint Committee on Cancer) stage IV solitary organ metastasis. In an independent cohort we compared cell densities, subpopulations spatial distribution tissue from LN or subcut 130 melanoma.Patients only brain bone had those soft Liver significantly lower T-cell infiltration than (p=0.0116 p=0.0252, respectively) respectively). T cells were further away (p=0.0335). displayed unique profiles, proportion programmed death protein-1+ all other (p<0.05), higher TIM-3+ (p=0.0004), (p=0.0082) (p=0.0128) Brain macrophage density (p=0.0105), (p=0.0095) (p<0.0001) Lung highest ligand-1+ macrophages total population, (p=0.0392).Liver reduced infiltrate metastases, which may account for poorer prognosis response rates Increased TIM-3 expression suggests inhibitor therapy potential therapeutic opportunity improve patient outcomes.