Macrophages Promote Circulating Tumor Cell-Mediated Local Recurrence Following Radiation Therapy in Immunosuppressed Patients

Rafat, Marjan; Aguilera, Todd A.; Vilalta, Marta; Bronsart, Laura L.; Soto, Luis A.; von Eyben, Rie; Golla, Meghana A.; Ahrari, Yasaman; Melemenidis, Stavros; Afghahi, Anosheh; Jenkins, Melissa J.; Kurian, Allison W.; Horst, Kathleen C.; Giaccia, Amato J.; Graves, Edward E.

- Add this to...
- Twitter
- Facebook
- Google Bookmarks
- LinkedIn

Macrophages Promote Circulating Tumor Cell-Mediated Local Recurrence Following Radiation Therapy in Immunosuppressed Patients

Published Date:

Jun 07 2018

Source:

Cancer Res. 78(15):4241-4252.

Language:

English

Public Access Version Available on: August 01, 2019

Please check back on the date listed above.

Details:

Personal Authors:

Rafat, Marjan ; Aguilera, Todd A. ; Vilalta, Marta ; Bronsart, Laura L. ; Soto, Luis A. ; ... More ▼

Keywords:

[+]

Pubmed ID:

29880480

Pubmed Central ID:

PMC6072588

Description:

Although radiotherapy (RT) decreases the incidence of locoregional recurrence in breast cancer, patients with triple-negative breast cancer (TNBC) have increased risk of local recurrence following breast-conserving therapy. The relationship between RT and local recurrence is unknown. Here, we tested the hypothesis that recurrence in some instances is due to the attraction of circulating tumor cells to irradiated tissues. To evaluate the effect of absolute lymphocyte count on local recurrence after RT in patients with TNBC, we analyzed radiation effects on tumor and immune cell recruitment to tissues in an orthotopic breast cancer model. Recurrent patients exhibited a prolonged low absolute lymphocyte count when compared with nonrecurrent patients following RT. Recruitment of tumor cells to irradiated normal tissues was enhanced in the absence of CD8| T cells. Macrophages (CD11b|F480|) preceded tumor cell infiltration and were recruited to tissues following RT. Tumor cell recruitment was mitigated by inhibiting macrophage infiltration using maraviroc, an FDA-approved CCR5 receptor antagonist. Our work poses the intriguing possibility that excessive macrophage infiltration in the absence of lymphocytes promotes local recurrence after RT. This combination thus defines a high-risk group of patients with TNBC.| This study establishes the importance of macrophages in driving tumor cell recruitment to sites of local radiation therapy and suggests that this mechanism contributes to local recurrence in women with TNBC that are also immunosuppressed.| http://cancerres.aacrjournals.org/content/canres/78/15/4241/F1.large.jpg |.

Document Type:

Journal Article

Collection(s):

CDC Public Access

Funding:

S10 OD018208/OD/NIH HHS/United States
HHSN261201000140C/CA/NCI NIH HHS/United States
K99 CA201304/CA/NCI NIH HHS/United States
P01 CA067166/CA/NCI NIH HHS/United States
HHSN261201000035C/CA/NCI NIH HHS/United States
T32 CA121940/CA/NCI NIH HHS/United States
R01 CA197136/CA/NCI NIH HHS/United States
U58 DP000807/DP/NCCDPHP CDC HHS/United States
HHSN261201000035I/CA/NCI NIH HHS/United States
UL1 RR025744/RR/NCRR NIH HHS/United States
HHSN261201000034C/CA/NCI NIH HHS/United States

Main Document Checksum:

[+]

Supporting Files:

No Additional Files

No Related Documents.

You May Also Like:

Potential infectious etiologies of atherosclerosis: a multifactorial perspective.

Personal Author:

O'Connor, S.; Taylor, C.; Campbell, L. A.; Epstein, S.; Libby, P.;

Published:

2001 Sep-Oct

Source:

Emerg Infect Dis. 7(5):780-788.

Description:

Coronary heart disease (CHD) contributes substantially to illness and death worldwide. Experimental studies demonstrate that infection can stimulate atherogenic processes. This review presents a spectrum of data regarding the link between CHD and inf...

File Type:

[PDF - 94.01 KB]
Interleukin 1-beta (IL-1β) production by innate cells following TLR stimulation correlates with TB recurrence in ART-treated HIV infected patients

Personal Author:

Thobakgale, Christina; Naidoo, Kewreshini; McKinnon, Lyle R.; Werner, Lise; Samsunder, Natasha; Karim, Salim Abdool; Ndung’u, Thumbi; Altfeld, Marcus; Naidoo, Kogieleum;

Published:

Feb 01 2017

Source:

J Acquir Immune Defic Syndr. 74(2):213-220.

Description:

Background : Tuberculosis (TB) remains a major cause of global morbidity and mortality, especially in the context of HIV co-infection, since immunity is not completely restored following antiretroviral therapy (ART). The identification of immune corr...

File Type:

[PDF - 858.19 KB]
Serum macrophage-derived chemokine/CCL22 levels are associated with glioma risk, CD4 T cell lymphopenia and survival time

Personal Author:

Zhou, Mi; Bracci, Paige M.; McCoy, Lucie S.; Hsuang, George; Wiemels, Joseph L.; Rice, Terri; Zheng, Shichun; Kelsey, Karl T.; Wrensch, Margaret R.; Wiencke, John K.;

Published:

Feb 02 2015

Source:

Int J Cancer. 137(4):826-836.

Description:

Defects in antigen presenting cell function have been implicated in glioma immunosuppression. We measured peripheral CCL22, a dendritic cell/macrophage derived T cell trafficking chemokine, in sera from 1,208 glioma cases and 976 controls to assess w...

File Type:

[PDF - 873.49 KB]
Data collection of primary central nervous system tumors; National Program of Cancer Registries training materials, 2004

Personal Author:

Clutter, Gayle

Corporate Author:

National Center for Chronic Disease Prevention and Health Promotion (U.S.), National Program of Cancer Registries.. Centers for Disease Control and Prevention (U.S.).

Published:

2004

Description:

This book is based on a training presentation prepared in part by the North American Association of Central Cancer Registries (NAACCR) and supported by contract 200-2001-00044 from the Centers for Disease Control and Prevention (CDC). We thank Shanno...

File Type:

[PDF - 2.30 MB]
The role of oxygen free radicals in occupational and environmental lung diseases.

Personal Author:

Vallyathan, V; Shi, X;

Published:

Feb 1997

Source:

Environ Health Perspect. 105(Suppl 1):165-177.

Description:

Oxygen free radicals and their metabolites, collectively described as reactive oxygen species (ROS), have been implicated in the pathogenesis of many diseases. The pulmonary system is particularly vulnerable to ROS-induced injury because of its conti...

File Type:

[PDF - 3.16 MB]