Imbalances in cellular immunological parameters in blood predetermine tumor onset in a natural mouse model of breast cancer
The development of new approaches to breast cancer (BC) early diagnosis is an important objective of modern oncology. Although the role of the immune system in cancer initiation process was experimentally well established, the prognostic value of cellular blood immunological parameters (CBIPs) for BC onset prediction was not demonstrated either in clinics or in mouse models. In this study, we focused on revealing informative CBIPs for mammary cancer (MC) onset prediction in the BLRB/BYRB mouse model with a high incidence of natural MC development. Blood samples were collected from 80 aging females of these original mouse strains, 12 basic CBIPs were estimated by flow cytometry. Then mice were followed up for 28 weeks, and the outcome of females (MC diagnosis, death without MC or MC-free survival) was registered. We estimated the patterns of changes in CBIPs with age and in accordance with the outcome. An increasing imbalance in 11 CBIPs during natural aging of females clearly resembled human immunosenescence phenomenon and several patterns corresponded to the results obtained on cancer-free members of BC-affected families. We stratified heterogeneous female population into middle-aged and old subgroups. Low NK-cell levels in middle-aged mice and low B-cell along with high T-helper levels in old mice distinguished females with developed MC from the other groups. We found a reliable correlation of several CBIPs with age at MC diagnosis and survival of cancer-bearing females. Thus, we demonstrated the predictive potential of CBIPs as a basis for the development of prognostic models for BC onset in clinics.
KeywordsBreast cancer Mouse model Immune system Cellular blood immunological parameters
Breast cancer (in humans)
Cellular blood immunological parameters
Mammary cancer (in mice)
DAA contributed in study design, flow cytometry, in vivo studies, data analysis, interpretation of results, and manuscript preparation. VVZ contributed in data analysis, interpretation of results, and manuscript drafting. SGS contributed in study design, histopathological analysis of mammary tumors, and manuscript drafting. EVM contributed in study design, in vivo studies, histopathological analysis to confirm or reject mammary cancer diagnosis, data analysis, interpretation of results, and manuscript preparation. All authors approved the final version of the manuscript.
No relevant funding.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All the animal experiments were conducted in accordance with the “Guide for the Care and Use of Laboratory Animals” (US Department of Health and Human Services, National Institute of Health Publication No 93–23, revised 1985) and were approved by the Institutional Animal Care and Use Committee (http://www.ibch.ru/downloads/documents/553/Institutional_Policy_on_the_Use_of_Laboratory_Animals.pdf). Animal research approval number: 155/2014.
Original mouse strains BLRB-Rb(8.17)1Iem and BYRB-Rb(8.17)1Iem were developed by Ekaterina Moiseeva  and have been bred and maintained at Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia since 1993.
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