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Background: After neoadjuvant chemotherapy (NAC), non-pathological complete response of breast cancer patients can benefit from tailored adjuvant chemotherapy. However, it is difficult to select patients with poorer prognosis for additional adjuvant chemotherapy to maximize the benefits. Our study aimed to explore whether the subtypes of tumor-infiltrating lymphocytes (TILs) in residual tumors (RT) is related to the prognosis of triple-negative breast cancer (TNBC) after NAC. Methods: Data from patients with primary TNBC consecutively diagnosed at the Breast Disease Center of Peking University First Hospital from 2008 to 2014 were retrieved, and the cases with RT in the breast after NAC were enrolled. TILs subtypes in RT were observed by double-staining immunohistochemistry, and counted with the median TILs value per square millimeter as the cut-off to define high versus low TILs density in each subtype. The relationships between the TIL density of each subgroup and the clinicopathological characteristics of the RT after NAC patients were analyzed by Fisher exact test. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank statistics. Results: A total of 37 eligible patients were included in this study, and the median follow-up period was 50 months (range 17–106 months). There was no significant correlation between the infiltrate density of CD4+, CD8+, CD20+, and CD68+ lymphocytes and clinic-pathological characteristics. Significantly better prognosis was observed in patients with high CD4+-TILs (DFS: P = 0.005, OS: P = 0.021) and high CD8+-TILs (DFS: P = 0.018) and low CD20+-TILs (OS: P = 0.042). Further analysis showed that patients with CD4+/CD20+ ratio greater than 1 (DFS: P = 0.001, OS: P = 0.002) or CD8+/CD20+ ratio greater than 1 (DFS: P = 0.009, OS: P = 0.022) had a better prognosis. Conclusions: Subtypes of TILs in RT is a potential predictive biomarker of survival in TNBC patients after NAC. Key words: Triple-negative breast cancer; Neoadjuvant chemotherapy; Residual tumors; Tumor-infiltrating lymphocyte subtypes

Several pieces of experimental evidence suggest that administration of anti-β amyloid (Aβ) vaccines, passive anti-Aβ antibodies or anti-inflammatory drugs can reduce Aβ deposition as well as associated cognitive/behavioral deficits in an Alzheimer disease (AD) transgenic (Tg) mouse model and, as such, may have some efficacy in human AD patients as well. In the investigation reported here an Aβ 1-42 peptide vaccine was administered to 16-month old APP+PS1 transgenic (Tg) mice in which Aβ deposition, cognitive memory deficits as well as levels of several pro-inflammatory cytokines were measured in response to the vaccination regimen. After vaccination, the anti-Aβ 1-42 antibody-producing mice demonstrated a significant reduction in the sera levels of 4 pro-inflammatory cytokines (TNF-α, IL-6, IL-1 α, and IL-12). Importantly, reductions in the cytokine levels of TNF-α and IL-6 were correlated with cognitive/behavioral improvement in the Tg mice. However, no differences in cerebral Aβ deposition in these mice were noted among the different control and experimental groups, i.e., Aβ 1-42 peptide vaccinated, control peptide vaccinated, or non-vaccinated mice. However, decreased levels of pro-inflammatory cytokines as well as improved cognitive performance were noted in mice vaccinated with the control peptide as well as those immunized with the Aβ 1-42 peptide. These findings suggest that reduction in pro-inflammatory cytokine levels in these mice may be utilized as an early biomarker for vaccination/treatment induced amelioration of cognitive deficits and are independent of Aβ deposition and, interestingly, antigen specific Aβ 1-42 vaccination. Since cytokine changes are typically related to T cell activation, the results imply that T cell regulation may have an important role in vaccination or other immunotherapeutic strategies in an AD mouse model and potentially in AD patients. Overall, these cytokine changes may serve as a predictive marker for AD development and progression as well as having potential therapeutic implications.

Background HIV-infected long-term non-progressor (LTNP) subjects can prevent viral replication and may harbor useful information for the development of both antibody and active vaccination treatments. In this study we used LTNP sera to examine the epitopes presented to the gp160 protein, and from this procedure we hope to elucidate potential biomarkers pertaining to the level of resistance a patient may have in developing AIDS after infection with HIV. We used five clinical sera samples from LTNP patients to identify common epitopes by ELISA; peptides with high binding to sera were selected and analyzed for conservation among HIV clades. Antibodies were generated against one identified epitope using a chimeric peptide in BALB/c mice, and both the sera from these mice and LTNP sera were tested for viral inhibition capabilities. Results A monoclonal antibody, CL3, against one identified epitope was used to compare these epitopes neutralizing capability. LTNP sera was also studied to determine chemokine/cytokine changes in these patients. The sera from LTNP patients 2, 3, 4, and 5 were identified as having the highest titers, and also significantly inhibited syncytia formation in vitro. Finally, the protein cytokine array demonstrated that I-309 and IGFBP-1 decreased in LTNPs, but levels of TIMP-1 and NAP-2 increased significantly. Conclusions Our results indicate that the use of LTNP samples may be a useful for identifying further anti-viral epitopes, and may be a possible predictor for determining if patients show higher resistances of converting the HIV infection to AIDS.