Immunological effects of Taxol and Adryamicin in breast cancer patients

Abstract

Antineoplastic chemotherapy still consists in the major first-line therapeutics against cancer. Several reports have described the immunomodulatory effects of these drugs based on in vitro treatment, but no previous data are known about these effects in patients and its association with immunological-mediated toxicity. In this study, we first characterize the immunological profile of advanced breast cancer patients treated with doxorubicin and paclitaxel protocols, immediately after chemotherapy infusion. Our findings included an immediate plasmatic reduction in IL-1, IL-10, and TNF-α levels in doxorubicin-treated patients, as well as high levels of IL-10 in paclitaxel patients. Further, it was demonstrated that both drugs led to leukocytes oxidative burst impairment. In vitro analysis was performed exposing healthy blood to both chemotherapics in the same concentration and time of exposition of patients, resulting in low IL-10 and high IL-1β in doxorubicin exposition, as low TNF-α and high IL-1 in paclitaxel treatment. Nitric oxide levels were not altered in both in vivo and in vitro treatments. In conclusion, our data revealed for the first time that the immediate effects of chemotherapy could be mediated by cytokines signaling in patients and that the results observed in patients could be a resultant of host immune cells activation.

Myeloid-derived suppressor cells are increased and correlated with type 2 immune responses, malnutrition, inflammation, and poor prognosis in patients with breast cancer

“…The results of multivariable analysis revealed that the risk of a poor prognosis is likely to be more dependent on MDSCs levels >1%, which were associated with a higher probability of mortality when adjusted for other potential prognostic factors. Certain anti-cancer chemotherapeutic agents, including gemcitabine, have been reported to alter MDSC levels, resulting in improvement of cellular immunocompetence (17,25). MDSC levels in the peripheral blood and in the pleural effusion of patients with metastatic breast cancer have been previously demonstrated to decrease following chemotherapy with gemcitabine (26).…”

MDR1 in immunity: friend or foe?

“…The hostile tumor micro-environment and its chemical composition must indeed shape the immune infiltrate, and MDR1 expression by anti-tumor immune cells may favor their preservation despite harsh environmental conditions. The immune infiltrate is also modulated by MDR1-associated anti-neoplastic agents, 90,101 and evaluation of MDR1 level on immune cells could be an indicator of these treatments’ effects.…”

Organic effects of associating paclitaxel with a lipid-based nanoparticle system on a nonhuman primate, <em>Cebus apella</em>

“…19 These data are in agreement with the literature, since the main adverse effects observed in treatment with commercial PTX are the following: adverse reactions relating to the bone marrow (alterations in leucocytes, thrombocytopenia, anemia induced by direct damage to erythrocytes), infections, hypersensitivity to hemorrhage, and neurotoxicity. 35,40,41 In relation to biochemical parameters, no relationship between PTX dose and alterations in hepatic function was demonstrated in patients without base hepatic alterations. Published research showed only rare relationships to hepatic necrosis and hepatic encephalopathy.…”