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.
N1 - Funding Information:
The authors would like to thank the MDACC TIL laboratory: Rahmatu Mansaray, Christopher Toth, Seth Wardell and Audrey Gonzalez. We would also like to thank all the clinical and research staff in the Melanoma Medical Oncology Department and Department of Surgical Oncology who contributed to the clinical TIL trial. This work was supported by the NIH/NCI Cancer Center Support Grant under award number P30CA016672 and used the Tissue Biospecimen and Pathology Resource. This work was also supported by the MD Anderson Institutional Research Grant Award #40080 (PI: S.P. Patel). A. Reuben is supported by the Kimberley Clarke Foundation Award for Scientific Achievement provided by MD Anderson's Odyssey Fellowship program.
Publisher Copyright:
© 2017 The Author(s). Published with license by Taylor & Francis Group
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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U2 - 10.1080/2162402X.2017.1321187
DO - 10.1080/2162402X.2017.1321187
M3 - Article
C2 - 28680759
AN - SCOPUS:85020296561
SN - 2162-4011
VL - 6
JO - OncoImmunology
JF - OncoImmunology
IS - 6
M1 - e1321187
ER -