scholarly journals Castration induces autoantibody and T cell responses that correlate with inferior outcomes in an androgen-dependent murine tumor model

2009 ◽  
Vol 125 (12) ◽  
pp. 2871-2878 ◽  
Author(s):  
Sara Hahn ◽  
Nancy J. Nesslinger ◽  
Robert J. Drapala ◽  
Mary Bowden ◽  
Paul S. Rennie ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Model ◽  
T Cell Responses ◽  
Cell Responses ◽  
Murine Tumor ◽  
Murine Tumor Model

scholarly journals CCRL2 promotes antitumor T-cell immunity via amplifying TLR4-mediated immunostimulatory macrophage activation

2021 ◽  
Vol 118 (16) ◽  
pp. e2024171118
Author(s):  
Wei Yin ◽  
Yihong Li ◽  
Yan Song ◽  
Jiarui Zhang ◽  
Chao Wu ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Growth ◽  
Tumor Model ◽  
T Cell Responses ◽  
T Cell Response ◽  
Tumor Rejection ◽  
Cell Responses ◽  
Cell Immunity ◽  
Potential Biomarker ◽  
Melanoma Growth

Macrophages are the key regulator of T-cell responses depending on their activation state. C-C motif chemokine receptor-like 2 (CCRL2), a nonsignaling atypical receptor originally cloned from LPS-activated macrophages, has recently been shown to regulate immune responses under several inflammatory conditions. However, whether CCRL2 influences macrophage function and regulates tumor immunity remains unknown. Here, we found that tumoral CCRL2 expression is a predictive indicator of robust antitumor T-cell responses in human cancers. CCRL2 is selectively expressed in tumor-associated macrophages (TAM) with immunostimulatory phenotype in humans and mice. Conditioned media from tumor cells could induce CCRL2 expression in macrophages primarily via TLR4, which is negated by immunosuppressive factors. Ccrl2−/− mice exhibit accelerated melanoma growth and impaired antitumor immunity characterized by significant reductions in immunostimulatory macrophages and T-cell responses in tumor. Depletion of CD8+ T cells or macrophages eliminates the difference in tumor growth between WT and Ccrl2−/− mice. Moreover, CCRL2 deficiency impairs immunogenic activation of macrophages, resulting in attenuated antitumor T-cell responses and aggravated tumor growth in a coinjection tumor model. Mechanically, CCRL2 interacts with TLR4 on the cell surface to retain membrane TLR4 expression and further enhance its downstream Myd88-NF-κB inflammatory signaling in macrophages. Similarly, Tlr4−/− mice exhibit reduced CCRL2 expression in TAM and accelerated melanoma growth. Collectively, our study reveals a functional role of CCRL2 in activating immunostimulatory macrophages, thereby potentiating antitumor T-cell response and tumor rejection, and suggests CCLR2 as a potential biomarker candidate and therapeutic target for cancer immunotherapy.

scholarly journals A transplantable tumor model allowing investigation of NY-BR-1-specific T cell responses in HLA-DRB1*0401 transgenic mice

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Krishna Das ◽  
David Eisel ◽  
Mathias Vormehr ◽  
Karin Müller-Decker ◽  
Adriane Hommertgen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Cell ◽  
Cell Line ◽  
In Silico ◽  
Cell Epitope ◽  
Tumor Model ◽  
T Cell Responses ◽  
T Cell Epitope ◽  
Cell Responses

Abstract Background NY-BR-1 has been described as a breast cancer associated differentiation antigen with intrinsic immunogenicity giving rise to endogenous T and B cell responses. The current study presents the first murine tumor model allowing functional investigation of NY-BR-1-specific immune responses in vivo. Methods A NY-BR-1 expressing tumor model was established in DR4tg mice based on heterotopic transplantation of stable transfectant clones derived from the murine H2 compatible breast cancer cell line EO771. Composition and phenotype of tumor infiltrating immune cells were analyzed by qPCR and FACS. MHC I binding affinity of candidate CTL epitopes predicted in silico was determined by FACS using the mutant cell line RMA-S. Frequencies of NY-BR-1 specific CTLs among splenocytes of immunized mice were quantified by FACS with an epitope loaded Db-dextramer. Functional CTL activity was determined by IFNγ catch or IFNγ ELISpot assays and statistical analysis was done applying the Mann Whitney test. Tumor protection experiments were performed by immunization of DR4tg mice with replication deficient recombinant adenovirus followed by s.c. challenge with NY-BR-1 expressing breast cancer cells. Results Our results show spontaneous accumulation of CD8+ T cells and F4/80+ myeloid cells preferentially in NY-BR-1 expressing tumors. Upon NY-BR-1-specific immunization experiments combined with in silico prediction and in vitro binding assays, the first NY-BR-1-specific H2-Db-restricted T cell epitope could be identified. Consequently, flow cytometric analysis with fluorochrome conjugated multimers showed enhanced frequencies of CD8+ T cells specific for the newly identified epitope in spleens of immunized mice. Moreover, immunization with Ad.NY-BR-1 resulted in partial protection against outgrowth of NY-BR-1 expressing tumors and promoted intratumoral accumulation of macrophages. Conclusion This study introduces the first H2-Db-resctricted CD8+ T cell epitope-specific for the human breast cancer associated tumor antigen NY-BR-1. Our novel, partially humanized tumor model enables investigation of the interplay between HLA-DR4-restricted T cell responses and CTLs within their joint attack of NY-BR-1 expressing tumors.

scholarly journals Lentiviral-mediated Foxp3 RNAi suppresses tumor growth of regulatory T cell-like leukemia in a murine tumor model

Gene Therapy ◽  
2010 ◽  
Vol 17 (8) ◽  
pp. 972-979 ◽  
Author(s):  
B-Y Tsai ◽  
J-L Suen ◽  
B-L Chiang
Keyword(s):  
T Cell ◽  
Tumor Growth ◽  
Regulatory T Cell ◽  
Tumor Model ◽  
Murine Tumor ◽  
Murine Tumor Model

scholarly journals Characterization of HPV18 E6-specific T cell responses and establishment of HPV18 E6-expressing tumor model

Vaccine ◽  
2017 ◽  
Vol 35 (31) ◽  
pp. 3850-3858 ◽  
Author(s):  
Ying Ma ◽  
Andrew Yang ◽  
Shiwen Peng ◽  
Jin Qiu ◽  
Emily Farmer ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Model ◽  
T Cell Responses ◽  
Cell Responses ◽  
Hpv18 E6

scholarly journals EBV Oncogene N-LMP1 Induces CD4 T Cell–Mediated Angiogenic Blockade in the Murine Tumor Model

2015 ◽  
Vol 194 (9) ◽  
pp. 4577-4587 ◽  
Author(s):  
Tzong-Shoon Wu ◽  
Lian-Chen Wang ◽  
Shu-Chen Liu ◽  
Ting-Yu Hsu ◽  
Chun-Yen Lin ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Model ◽  
Cd4 T Cell ◽  
Murine Tumor ◽  
Murine Tumor Model

Author response for "Naturally processed HLA‐DR3‐restricted HHV‐6b peptides are recognized broadly with polyfunctional and cytotoxic CD4 T cell responses"

2019 ◽  
Author(s):  
Aniuska Becerra‐Artiles ◽  
John Cruz ◽  
John D. Leszyk ◽  
John Sidney ◽  
Alessandro Sette ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Author Response ◽  
Cell Responses ◽  
Hla Dr3

Malarial phosphorylated antigens activating human γδ T cell responses

1997 ◽  
Vol 56 (1-3) ◽  
pp. 425
Author(s):  
R Poupot
Keyword(s):  
T Cell ◽  
T Cell Responses ◽  
Γδ T Cell ◽  
Cell Responses
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