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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 9/2013

01-09-2013 | Melanomas

Immunological Insights from Patients Undergoing Surgery on Ipilimumab for Metastatic Melanoma

Authors: David E. Gyorki, MBBS MD, Jianda Yuan, MD PhD, Zhenyu Mu, PhD, Bushra Zaidi, PhD, Melissa Pulitzer, MD, Klaus Busam, MD, Mary S. Brady, MD FACS, Daniel G. Coit, MD FACS, James P. Allison, PhD, Jedd D. Wolchok, MD PhD, Charlotte E. Ariyan, MD PhD FACS

Published in: Annals of Surgical Oncology | Issue 9/2013

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Abstract

Background

The tumor microenvironment after treatment with ipilimumab is not well described. Furthermore, the safety of surgery for patients being treated with ipilimumab for metastatic melanoma has not been well reported. This study analyzed the safety of surgery and the immune phenotype of tumors resected while on ipilimumab.

Methods

From our prospective melanoma database, we identified patients undergoing surgery for any indication within 30 days of receiving a dose of induction ipilimumab or while on maintenance ipilimumab therapy. Surgical toxicity was graded 1–5 by the Clavien classification. Tumor-infiltrating lymphocytes were classified by flow cytometry and compared with peripheral blood.

Results

23 patients were identified who underwent 34 operations a median of 27 weeks after initiation of ipilimumab (1–123 weeks). Subcutaneous resections were the most frequent, followed by intra-abdominal and nodal procedures. Grade 1 or 2 wound complications were seen in 22 % of patients. No Grade 3–5 complications were seen. Analysis of the T cell infiltrate and matched peripheral blood from ten patients showed an elevated % of CD4+FOXP3+ T-regulatory cells and a 2.8-fold lower ratio of CD8+/CD4+FOXP3+ in the tumor compared with blood (p = 0.02). In addition, all CD8+ T cells had a higher expression of PD-1 in the tumor, compared with peripheral blood.

Conclusions

Surgery for patients on ipilimumab is safe. This study highlights the immunosuppressive phenotype in tumors not responding to immunotherapy. The high percentage of T-regulatory cells and low T-effector cells in progressive tumors suggests a possible mechanism of immune escape.
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Metadata
Title
Immunological Insights from Patients Undergoing Surgery on Ipilimumab for Metastatic Melanoma
Authors
David E. Gyorki, MBBS MD
Jianda Yuan, MD PhD
Zhenyu Mu, PhD
Bushra Zaidi, PhD
Melissa Pulitzer, MD
Klaus Busam, MD
Mary S. Brady, MD FACS
Daniel G. Coit, MD FACS
James P. Allison, PhD
Jedd D. Wolchok, MD PhD
Charlotte E. Ariyan, MD PhD FACS
Publication date
01-09-2013
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 9/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-013-2999-1

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