Format

Send to

Choose Destination
Cancer Discov. 2016 Aug;6(8):827-37. doi: 10.1158/2159-8290.CD-15-1545. Epub 2016 Jun 14.

Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade.

Author information

1
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
2
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
3
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
4
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
5
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
6
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
7
Department of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
8
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
9
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
10
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
11
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
12
Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas.
13
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts.
14
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
15
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. JWargo@mdanderson.org.

Abstract

Immune checkpoint blockade represents a major breakthrough in cancer therapy; however, responses are not universal. Genomic and immune features in pretreatment tumor biopsies have been reported to correlate with response in patients with melanoma and other cancers, but robust biomarkers have not been identified. We studied a cohort of patients with metastatic melanoma initially treated with cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) blockade (n = 53) followed by programmed death-1 (PD-1) blockade at progression (n = 46), and analyzed immune signatures in longitudinal tissue samples collected at multiple time points during therapy. In this study, we demonstrate that adaptive immune signatures in tumor biopsy samples obtained early during the course of treatment are highly predictive of response to immune checkpoint blockade and also demonstrate differential effects on the tumor microenvironment induced by CTLA4 and PD-1 blockade. Importantly, potential mechanisms of therapeutic resistance to immune checkpoint blockade were also identified.

SIGNIFICANCE:

These studies demonstrate that adaptive immune signatures in early on-treatment tumor biopsies are predictive of response to checkpoint blockade and yield insight into mechanisms of therapeutic resistance. These concepts have far-reaching implications in this age of precision medicine and should be explored in immune checkpoint blockade treatment across cancer types. Cancer Discov; 6(8); 827-37. ©2016 AACR.See related commentary by Teng et al., p. 818This article is highlighted in the In This Issue feature, p. 803.

Comment in

PMID:
27301722
PMCID:
PMC5082984
DOI:
10.1158/2159-8290.CD-15-1545
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

No other potential conflicts of interest were disclosed.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center