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Oncoimmunology. 2016 Feb 2;5(3):e1136044. eCollection 2016 Mar.

Distinct clinical patterns and immune infiltrates are observed at time of progression on targeted therapy versus immune checkpoint blockade for melanoma.

Author information

1
Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
2
Department of Surgical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
3
Genomic Medicine, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
4
Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
5
Pathology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
6
Division of Medical Oncology, Massachusetts General Hospital , Boston, MA, USA.
7
Immunology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
8
Translational Molecular Pathology, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
9
Department of Cell, Developmental and Cancer Biology and Knight Cancer Institute, Oregon Health and Science University , Portland, OR, USA.
10
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School , Boston, MA, USA.
11
Stem Cell Transplantation, University of Texas MD Anderson Cancer Center , Houston, TX, USA.
12
Immunology, University of Texas MD Anderson Cancer Center, Houston, TX, USA; Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Abstract

We have made major advances in the treatment of melanoma through the use of targeted therapy and immune checkpoint blockade; however, clinicians are posed with therapeutic dilemmas regarding timing and sequence of therapy. There is a growing appreciation of the impact of antitumor immune responses to these therapies, and we performed studies to test the hypothesis that clinical patterns and immune infiltrates differ at progression on these treatments. We observed rapid clinical progression kinetics in patients on targeted therapy compared to immune checkpoint blockade. To gain insight into possible immune mechanisms behind these differences, we performed deep immune profiling in tumors of patients on therapy. We demonstrated low CD8+ T-cell infiltrate on targeted therapy and high CD8+ T-cell infiltrate on immune checkpoint blockade at clinical progression. These data have important implications, and suggest that antitumor immune responses should be assessed when considering therapeutic options for patients with melanoma.

KEYWORDS:

BRAF; CTLA-4; Immune checkpoint blockade; PD-1; melanoma; targeted therapy

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