The modulation of adaptive immune response by oncogene K-ras; mouse model of ovarian cancer

2015 ◽  
Vol 112 ◽  
pp. 132
Author(s):  
Juri Takahashi ◽  
Kei Kawana ◽  
Ayumi Taguchi ◽  
Mitsuyo Yoshida ◽  
Hiroe Nakamura ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
Mouse Model ◽  
Adaptive Immune Response ◽  
Adaptive Immune

scholarly journals Evidence for a role of adaptive immune response in the disease pathogenesis of the MPTP mouse model of Parkinson's disease

Glia ◽  
2015 ◽  
Vol 64 (3) ◽  
pp. 386-395 ◽  
Author(s):  
Heather L. Martin ◽  
Matteo Santoro ◽  
Sarah Mustafa ◽  
Gernot Riedel ◽  
John V. Forrester ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Immune Response ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Adaptive Immune Response ◽  
Disease Pathogenesis ◽  
Adaptive Immune

scholarly journals Peroral Ciprofloxacin Therapy Impairs the Generation of a Protective Immune Response in a Mouse Model for Salmonella enterica Serovar Typhimurium Diarrhea, while Parenteral Ceftriaxone Therapy Does Not

2012 ◽  
Vol 56 (5) ◽  
pp. 2295-2304 ◽  
Author(s):  
Kathrin Endt ◽  
Lisa Maier ◽  
Rina Käppeli ◽  
Manja Barthel ◽  
Benjamin Misselwitz ◽  
...  
Keyword(s):  
Immune Response ◽  
Mouse Model ◽  
Antibiotic Treatment ◽  
Salmonella Enterica ◽  
Adaptive Immune Response ◽  
Content Type ◽  
Fecal Shedding ◽  
Treatment Regimens ◽  
Adaptive Immune ◽  
Serovar Typhimurium

ABSTRACTNontyphoidalSalmonella(NTS) species cause self-limiting diarrhea and sometimes severe disease. Antibiotic treatment is considered only in severe cases and immune-compromised patients. The beneficial effects of antibiotic therapy and the consequences for adaptive immune responses are not well understood. We used a mouse model forSalmonelladiarrhea to assess the effects ofper ostreatment with ciprofloxacin (15 mg/kg of body weight intragastrically 2 times/day, 5 days) or parenteral ceftriaxone (50 mg/kg intraperitoneally, 5 days), two common drugs used in human patients. The therapeutic and adverse effects were assessed with respect to generation of a protective adaptive immune response, fecal pathogen excretion, and the emergence of nonsymptomatic excreters. In the mouse model, both therapies reduced disease severity and reduced the level of fecal shedding. In line with clinical data, in most animals, a rebound of pathogen gut colonization/fecal shedding was observed 2 to 12 days after the end of the treatment. Yet, levels of pathogen shedding and frequency of appearance of nonsymptomatic excreters did not differ from those for untreated controls. Moreover, mice treated intraperitoneally with ceftriaxone developed an adaptive immunity protecting the mice from enteropathy in wild-typeSalmonella entericaserovar Typhimurium challenge infections. In contrast, the mice treated intragastrically with ciprofloxacin were not protected. Thus, antibiotic treatment regimens can disrupt the adaptive immune response, but treatment regimens may be optimized in order to preserve the generation of protective immunity. It might be of interest to determine whether this also pertains to human patients. In this case, the mouse model might be a tool for further mechanistic studies.

scholarly journals Giving blood: a new role for CD40 in tumorigenesis

2006 ◽  
Vol 203 (11) ◽  
pp. 2409-2412 ◽  
Author(s):  
Stephan Bergmann ◽  
Pier Paolo Pandolfi
Keyword(s):  
Immune Response ◽  
Endothelial Cells ◽  
B Cells ◽  
Mouse Model ◽  
Transgenic Mice ◽  
Early Stage ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Novel Therapeutic

CD40 was initially identified as a receptor expressed by B cells that is crucial for inducing an effective adaptive immune response. CD40 was subsequently shown to be expressed by endothelial cells and to promote angiogenesis. New data now show that in tumor-prone transgenic mice, CD40-mediated neovascularization is essential for early stage tumorigenicity. This suggests, at least in this mouse model, that CD40 has an important role in the angiogenic process that is coupled to carcinogenesis, a finding that could lead to novel therapeutic opportunities.

scholarly journals Chemokines are Underestimated in Preventing the Metastasizing and the Immune Elimination of Ovarian Cancer

2019 ◽  
Author(s):  
Ruurd Torensma ◽  
Petra Zusterzeel
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Adaptive Immune Response ◽  
Inhibitory Response ◽  
T Cell Response ◽  
Activated T Cells ◽  
Adaptive Immune

Nowadays the positive immune involvement in the eradication of tumor cells is assigned to the adaptive immune response. By awakening of in vivo responding T cells that are suppressed by the tumor and prevents immunological cure of the cancer. The adaptive immune response is a complex of different cells and protein molecules. Normally activated T cells are well-ordered by several late occurring inhibitors to contain the response to the unknown invaders and spare the normal cells. The tumor strengthens this inhibitory response to escape from immune elimination. Immunotherapy is to unleash the full capacity of the adaptive immune system by blocking this inhibitor response by monoclonal antibodies but with the potential drawback of autoimmune phenomena. Seen the success of the immunotherapy another feature of the immune system is overlooked. Cytokines and chemokines became in oblivion after their suspected necrosis of the tumor (TNF) did not fulfil their initial hope. When patients seek help for their complaints the ovarian cancer is in most cases already metastasized to the peritoneum and omentum. Here, we show that on the one hand chemokines produced by Th2, CD8 and NK cells inhibit cancer spreading and thus leads to a better operability and thus better survival. On the other hand, chemokine receptors are expressed by the tumor that are a decoy by binding chemokines that normally should attract antigen cross-presenting dendritic cells, which start an adaptive T cell response.

scholarly journals Clinical outcomes of prexasertib monotherapy in recurrent BRCA wild-type high-grade serous ovarian cancer involve innate and adaptive immune responses

2020 ◽  
Vol 8 (2) ◽  
pp. e000516
Author(s):  
Erika J Lampert ◽  
Ashley Cimino-Mathews ◽  
Joo Sang Lee ◽  
Jayakumar Nair ◽  
Min-Jung Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
Adaptive Immune Response ◽  
Cell Cycle Checkpoint ◽  
High Grade ◽  
Blood Samples ◽  
Adaptive Immune ◽  
Cycle Checkpoint

BackgroundPreclinical data suggest cell cycle checkpoint blockade may induce an immunostimulatory tumor microenvironment. However, it remains elusive whether immunomodulation occurs in the clinical setting. To test this, we used blood and fresh tissue samples collected at baseline and post therapy from a phase II trial of the cell cycle checkpoint 1 inhibitor (CHK1i) prexasertib in recurrent ovarian cancer.MethodsPaired blood samples and fresh core biopsies, taken before treatment was started at baseline (cycle 1 day 1 (C1D1)) and post second dose on day 15 of cycle 1 (C1D15), were collected. To evaluate changes in the immune responses after treatment, multiparametric flow cytometry for DNA damage markers and immune cell subsets was performed on paired blood samples. RNA sequencing (RNAseq) of paired core biopsies was also analyzed. Archival tissue immune microenvironment was evaluated with immunohistochemistry. All correlative study statistical analyses used two-sided significance with a cut-off of p=0.05.ResultsFlow cytometric analysis showed significantly increased γ-H2AX staining after CHK1i treatment, accompanied by increased monocyte populations, suggestive of an activated innate immune response (median 31.6% vs 45.6%, p=0.005). Increased expressions of immunocompetence marker HLA-DR (Human Leukocyte Antigen DR antigen) on monocytes and of TBK1, a marker of STING (stimulator of interferon genes) pathway activation, in biopsies were associated with improved progression-free survival (PFS) (9.25 vs 3.5 months, p=0.019; 9 vs 3 months, p=0.003, respectively). Computational analysis of RNAseq data indicated increased infiltration of tumor niches by naïve B-cells and resting memory T-cells, suggestive of a possibly activated adaptive immune response, and greater T-reg infiltration after treatment correlated with worse PFS (9.25 vs 3.5 months, p=0.007). An immunosuppressive adaptive immune response, perhaps compensatory, was also observed on flow cytometry, including lymphodepletion of total peripheral CD4+ and CD8+T cells after CHK1i and an increase in the proportion of T-regs among these T-cells. Additionally, there was a trend of improved PFS with greater tumor-infiltrating lymphocytes (TILs) in archival tissues (13.7 months >30% TILs vs 5.5 months ≤30% TILs, p=0.05).ConclusionOur study demonstrates that a favorable clinical response in high-grade serous ovarian carcinoma patients treated with CHK1i is possibly associated with enhanced innate and adaptive immunity, requiring further mechanistic studies. It is supportive of current efforts for a clinical development strategy for therapeutic combinations with immunotherapy in ovarian cancer.

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