Age-related effects on tumor growth and metastatic progression: impact on immune populations in distant sites
LIBONI C. 1,2,3,4, BOCHLER L. 1,2,3,4, COLIN F. 1,2,3,4, LARNICOL A. 1,2,3,4, MITTELHEISSER V. 1,2,3,4, OSMANI N. 1,2,3,4, HYENNE V. 1,2,3,4,5, LEFEBVRE O. 1,2,3,4, GOETZ J. 1,2,3,4
1 Unistra, Strasbourg, France; 2 Tumor Biomechanics INSERM UMR_S1109, Strasbourg, France; 3 Fédération de Médecine Translationnelle de Strasbourg (FMTS), Strasbourg, France; 4 Equipe Labellisée Ligue Contre le Cancer, Strasbourg, France; 5 CNRS, SNC5055, Strasbourg, France
Aging has been widely recognized as an additional risk factor for cancer prompting its insurgence, recurrence and the development of drug-resistance. With the population median age increasing in developed countries, a better characterization of the age-related impact on cancer is of outmost urgency. Among cancer types, triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer presenting an increased metastasis in elderlies and resistance to therapies, the latter mostly linked to the accumulation of senescent cells. As senescence (defined as the permanent arrest in cell proliferation associated to a specific secretory phenotype-SASP) is pivotal in the aging process, our study will investigate its role and the overall aging-impact in in TNBC. We experimentally probed TNBC progression in murine orthotopic and experimental metastasis model in parallel at: 3 months (young), 10 months (middle-age) and 18 months (geriatric). Our results suggest no age-related effect in tumor burden in the orthotopic model while blood cell counts revealed alterations in neutrophils, monocytes/macrophages and lymphocytes populations among the different groups. Interestingly, flow cytometry-based lung immunophenotyping demonstrate an increase in interstitial macrophages and neutrophils with a concomitant decrease in alveolar macrophages and B cells restricted to tumor-bearing mice. On the contrary, age impacts metastatic outgrowth in the experimental metastasis model, without affecting lungs major immune cells populations. Nevertheless, immune populations in blood (monocytes, lymphocytes and neutrophils) result affected suggesting the existence of some impact at systemic level. Current experiments aim at better characterizing the impact of age on the differences observed in our animal models pointing mainly at the role of immune cells subtypes highlighted in distant metastatic sites. Overall, this analysis will provide new hints toward the re-shaping of therapeutic solutions according to age in TNBC and, potentially, highlight new targets.