TY - JOUR
T1 - Parallel profiling of immune infiltrate subsets in uveal melanoma versus cutaneous melanoma unveils similarities and differences
T2 - A pilot study
AU - Qin, Yong
AU - Petaccia de Macedo, Mariana
AU - Reuben, Alexandre
AU - Forget, Marie Andrée
AU - Haymaker, Cara
AU - Bernatchez, Chantale
AU - Spencer, Christine N.
AU - Gopalakrishnan, Vancheswaran
AU - Reddy, Sujan
AU - Cooper, Zachary A.
AU - Fulbright, Orenthial J.
AU - Ramachandran, Renjith
AU - Wahl, Arely
AU - Flores, Esteban
AU - Thorsen, Shawne T.
AU - Tavera, Rene J.
AU - Conrad, Claudius
AU - Williams, Michelle D.
AU - Tetzlaff, Michael T.
AU - Wang, Wei Lien
AU - Gombos, Dan S.
AU - Esmaeli, Bita
AU - Amaria, Rodabe N.
AU - Hwu, Patrick
AU - Wargo, Jennifer A.
AU - Lazar, Alexander J.
AU - Patel, Sapna P.
PY - 2017/6/3
Y1 - 2017/6/3
N2 - 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.
AB - 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.
KW - Cutaneous melanoma
KW - immune profile
KW - tumor infiltrating lymphocytes
KW - uveal melanoma
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UR - http://www.scopus.com/inward/citedby.url?scp=85020296561&partnerID=8YFLogxK
U2 - 10.1080/2162402X.2017.1321187
DO - 10.1080/2162402X.2017.1321187
M3 - Article
C2 - 28680759
AN - SCOPUS:85020296561
VL - 6
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 6
M1 - e1321187
ER -