Minimal changes in the systemic immune response after nephrectomy of localized renal masses

Gal Wald; Kerri T Barnes; Megan T Bing; Timothy P Kresowik; Ann Tomanek-Chalkley; Tamara A Kucaba; Thomas S Griffith; James A Brown; Lyse A Norian

doi:10.1016/j.urolonc.2014.01.023

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Minimal changes in the systemic immune response after nephrectomy of localized renal masses

Journal article

Open access

Peer reviewed

Minimal changes in the systemic immune response after nephrectomy of localized renal masses

Gal Wald, Kerri T Barnes, Megan T Bing, Timothy P Kresowik, Ann Tomanek-Chalkley, Tamara A Kucaba, Thomas S Griffith, James A Brown and Lyse A Norian

Urologic oncology, Vol.32(5), pp.589-600

07/2014

DOI: 10.1016/j.urolonc.2014.01.023

PMCID: PMC4124886

PMID: 24768357

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Abstract

Renal cell carcinoma (RCC) is an immunogenic tumor, and multiple immunostimulatory therapies are in use or under development for patients with inoperable tumors. However, a major drawback to the use of immunotherapy for RCC is that renal tumors are also immunosuppressive. As a result, current immunotherapies are curative in<10% of patients with RCC. To better understand the systemic immune response to RCC, we performed a comprehensive examination of the leukocyte and cytokine/chemokine composition in the peripheral blood of patients with localized clear cell renal tumors pre- and post-nephrectomy. Peripheral blood samples were taken from 53 consented subjects with renal masses before cytoreductive nephrectomy and again at clinic visits approximately 30 days after nephrectomy. Samples were also obtained from 10 healthy age- and gender-matched controls. Blood samples from clear cell RCC subjects were analyzed by multi-parameter flow cytometry to determine leukocyte subset composition and multiplex array to evaluate plasma proteins. Pre-nephrectomy, clear cell tumors were associated with systemic accumulations of both "exhausted" CD8+ T cells, as indicated by surface BTLA expression, and monocytic CD14(+)HLA-DR(neg)CD33(+) myeloid-derived suppressor cells (MDSC). Subjects with T3 clear cell RCC also had a unique pro-tumorigenic and inflammatory cytokine/chemokine profile characterized by high serum concentrations of IL-1β, IL-2, IL-5, IL-7, IL-8, IL-17, TNF-α, MCP-1 and MIP-1β. At an early post-nephrectomy time point (~30 d), we found the systemic immune response to be largely unaltered. The only significant change was a decrease in the mean percentage of circulating BTLA(+)CD8(+) T cells. All other cellular and soluble immune parameters we examined were unaltered by the removal of the primary tumor. In the first month following surgery, nephrectomy may relieve systemic CD8 T cell exhaustion marked by BTLA expression, but continuing inflammation and MDSC presence likely counteract this positive effect. Future determination of how this systemic immune signature becomes altered during metastatic progression could provide novel targets for neoadjuvant immunotherapy in RCC.

Chemokines - blood

Immunotherapy - methods

Humans

Immunosuppressive Agents - therapeutic use

Middle Aged

Kidney Neoplasms - immunology

Carcinoma, Renal Cell - surgery

Male

Carcinoma, Renal Cell - immunology

Kidney Neoplasms - blood

Nephrectomy - methods

Kidney Neoplasms - surgery

Neoplasm Metastasis

Flow Cytometry

Aged, 80 and over

Adult

Female

Cytokines - blood

Leukocytes - cytology

Carcinoma, Renal Cell - blood

Treatment Outcome

Inflammation

Disease Progression

Aged

CD8-Positive T-Lymphocytes - immunology

Details

Title: Subtitle: Minimal changes in the systemic immune response after nephrectomy of localized renal masses
Creators: Gal Wald - Department of Urology, The University of Iowa Carver College of Medicine, Iowa City, IA
Kerri T Barnes - Department of Urology, The University of Iowa Carver College of Medicine, Iowa City, IA
Megan T Bing - Department of Urology, The University of Iowa Carver College of Medicine, Iowa City, IA
Timothy P Kresowik - Department of Urology, The University of Iowa Carver College of Medicine, Iowa City, IA
Ann Tomanek-Chalkley - Department of Urology, The University of Iowa Carver College of Medicine, Iowa City, IA
Tamara A Kucaba - Department of Urology, University of Minnesota, Minneapolis, MN
Thomas S Griffith - Masonic Cancer Center, University of Minnesota, Minneapolis, MN
James A Brown - Holden Comprehensive Cancer Center, The University of Iowa Carver College of Medicine, Iowa City, IA
Lyse A Norian - Center for Immunology, The University of Iowa Carver College of Medicine, Iowa City, IA
Resource Type: Journal article
Publication Details: Urologic oncology, Vol.32(5), pp.589-600
DOI: 10.1016/j.urolonc.2014.01.023
PMID: 24768357
PMCID: PMC4124886
NLM abbreviation: Urol Oncol
ISSN: 1078-1439
eISSN: 1873-2496
Publisher: United States
Grant note: CA181088-01 / NCI NIH HHS CA109446 / NCI NIH HHS R01 CA109446 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R01 CA181088 / NCI NIH HHS
Language: English
Date published: 07/2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiation Oncology; Urology
Record Identifier: 9984051555902771

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