Chemotherapy Necessitates Increased Immune Control of HHVs: A Cause of Persistent Inflammation Enabling Protracted Fatigue in Breast Cancer Survivors.

摘要

This work hypothesizes that chemotherapy can permanently alter the balance between the immune system and chronic herpes virus infections. We predicted that herpes virus-driven inflammatory cytokines exacerbate cancer treatment related fatigue (CTRF). Here we report the significant finding that high C-reactive protein (CRP) levels, indicative of underlying inflammatory milieu, are predictive of fatigue in a retrospective cohort of n=108 breast cancer survivors. Survivor HHV burden, as assessed by number of viruses carried by a subject was not predictive of fatigue or CRP levels. Further, type of HHVs carried by subjects was not predictive of fatigue or CRP levels. We further sought to assess CRP levels, as a predictive biomarker of breast cancer survivor fatigue, in women actively undergoing chemotherapy treatment for breast cancer. In a cohort of n=20 subjects we found a significant increase in CRP levels between EBV+ and EBV/CMV double positive subjects. Moreover, EBV/CMV double positive individuals showed increased serum IFN- . High IFN- levels were significantly associated with enhanced serum hs-CRP. Taken together, fatigued breast cancer survivors had higher levels of hs-CRP. Similarly, CMV/EBV double positive breast cancer patients undergoing chemotherapy showed higher hs-CRP levels than CMV-/EBV+ subjects. CRP and viral status in subjects actively undergoing breast cancer therapy predict the patient population at risk for CTRF.