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Unveiling the tumor immune microenvironment of organ-specific melanoma metastatic sites.
Conway, Jordan W; Rawson, Robert V; Lo, Serigne; Ahmed, Tasnia; Vergara, Ismael A; Gide, Tuba N; Attrill, Grace Heloise; Carlino, Matteo S; Saw, Robyn P M; Thompson, John F; Spillane, Andrew J; Shannon, Kerwin F; Shivalingam, Brindha; Menzies, Alexander Maxwell; Wilmott, James S; Long, Georgina V; Scolyer, Richard A; Pires da Silva, Ines.
Afiliação
  • Conway JW; Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
  • Rawson RV; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
  • Lo S; Charles Perkins Centre, The University of Sydney, Sydney, New south Wales, Australia.
  • Ahmed T; Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
  • Vergara IA; Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and NSW Health Pathology, Sydney, New South Wales, Australia.
  • Gide TN; Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
  • Attrill GH; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
  • Carlino MS; Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
  • Saw RPM; Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
  • Thompson JF; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
  • Spillane AJ; Charles Perkins Centre, The University of Sydney, Sydney, New south Wales, Australia.
  • Shannon KF; Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
  • Shivalingam B; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
  • Menzies AM; Charles Perkins Centre, The University of Sydney, Sydney, New south Wales, Australia.
  • Wilmott JS; Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
  • Long GV; Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.
  • Scolyer RA; Charles Perkins Centre, The University of Sydney, Sydney, New south Wales, Australia.
  • Pires da Silva I; Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
J Immunother Cancer ; 10(9)2022 09.
Article em En | MEDLINE | ID: mdl-36096531
ABSTRACT

BACKGROUND:

The liver is a known site of resistance to immunotherapy and the presence of liver metastases is associated with shorter progression-free and overall survival (OS) in melanoma, while lung metastases have been associated with a more favorable outcome. There are limited data available regarding the immune microenvironment at different anatomical sites of melanoma metastases. This study sought to characterize and compare the tumor immune microenvironment of liver, brain, lung, subcutaneous (subcut) as well as lymph node (LN) melanoma metastases.

METHODS:

We analyzed OS in 1924 systemic treatment-naïve patients with AJCC (American Joint Committee on Cancer) stage IV melanoma with a solitary site of organ metastasis. In an independent cohort we analyzed and compared immune cell densities, subpopulations and spatial distribution in tissue from liver, lung, brain, LN or subcut sites from 130 patients with stage IV melanoma.

RESULTS:

Patients with only liver, brain or bone metastases had shorter OS compared to those with lung, LN or subcutaneous and soft tissue metastases. Liver and brain metastases had significantly lower T-cell infiltration than lung (p=0.0116 and p=0.0252, respectively) and LN metastases (p=0.0116 and p=0.0252, respectively). T cells were further away from melanoma cells in liver than lung metastases (p=0.0335). Liver metastases displayed unique T-cell profiles, with a significantly lower proportion of programmed cell death protein-1+ T cells compared to all other anatomical sites (p<0.05), and a higher proportion of TIM-3+ T cells compared to LN (p=0.0004), subcut (p=0.0082) and brain (p=0.0128) metastases. Brain metastases had a lower macrophage density than subcut (p=0.0105), liver (p=0.0095) and lung (p<0.0001) metastases. Lung metastases had the highest proportion of programmed death ligand-1+ macrophages of the total macrophage population, significantly higher than brain (p<0.0001) and liver metastases (p=0.0392).

CONCLUSIONS:

Liver and brain melanoma metastases have a significantly reduced immune infiltrate than lung, subcut and LN metastases, which may account for poorer prognosis and reduced immunotherapy response rates in patients with liver or brain metastases. Increased TIM-3 expression in liver metastases suggests TIM-3 inhibitor therapy as a potential therapeutic opportunity to improve patient outcomes.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Neoplasias Hepáticas / Neoplasias Pulmonares / Melanoma Limite: Humans Idioma: En Revista: J Immunother Cancer Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Austrália
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Neoplasias Hepáticas / Neoplasias Pulmonares / Melanoma Limite: Humans Idioma: En Revista: J Immunother Cancer Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Austrália