OncoImmunology (Jun 2017)

Parallel profiling of immune infiltrate subsets in uveal melanoma versus cutaneous melanoma unveils similarities and differences: A pilot study

  • Yong Qin,
  • Mariana Petaccia de Macedo,
  • Alexandre Reuben,
  • Marie-Andrée Forget,
  • Cara Haymaker,
  • Chantale Bernatchez,
  • Christine N. Spencer,
  • Vancheswaran Gopalakrishnan,
  • Sujan Reddy,
  • Zachary A. Cooper,
  • Orenthial J. Fulbright,
  • Renjith Ramachandran,
  • Arely Wahl,
  • Esteban Flores,
  • Shawne T. Thorsen,
  • Rene J. Tavera,
  • Claudius Conrad,
  • Michelle D. Williams,
  • Michael T. Tetzlaff,
  • Wei-Lien Wang,
  • Dan S. Gombos,
  • Bita Esmaeli,
  • Rodabe N. Amaria,
  • Patrick Hwu,
  • Jennifer A. Wargo,
  • Alexander J. Lazar,
  • Sapna P. Patel

DOI
https://doi.org/10.1080/2162402X.2017.1321187
Journal volume & issue
Vol. 6, no. 6

Abstract

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The low response rates to immunotherapy in uveal melanoma (UM) sharply contrast with reputable response rates in cutaneous melanoma (CM) patients. To characterize the mechanisms responsible for resistance to immunotherapy in UM, we performed immune profiling in tumors from 10 metastatic UM patients and 10 metastatic CM patients by immunohistochemistry (IHC). Although there is no difference in infiltrating CD8+ T cells between UM and CM, a significant decrease in programmed death-1 (PD-1)-positive lymphocytes was observed and lower levels of programmed death ligand-1 (PD-L1) in UM metastases compared with CM metastases. Tumors from metastatic UM patients showed a lower success rate of tumor-infiltrating lymphocyte (TIL) growth compared with metastatic CM (45% vs. 64% success), with a significantly lower quantity of UM TIL expanded overall. These studies suggest that UM and CM are immunologically distinct, and provide potential explanation for the impaired success of immunotherapy in UM.

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