scholarly journals CD8+ T cell immunity blocks the metastasis of carcinogen-exposed breast cancer

2021 ◽  
Vol 7 (25) ◽  
pp. eabd8936
Author(s):  
Kaiwen Li ◽  
Tiancheng Li ◽  
Zhaoyi Feng ◽  
Mei Huang ◽  
Lei Wei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Cytolytic Activity ◽  
T Cell Immunity ◽  
Breast Cancers ◽  
Mutational Burden ◽  
Cell Immunity ◽  
Carcinogen Exposure

The link between carcinogen exposure and cancer immunogenicity is unclear. Single exposure to 12-dimethylbenz[a]anthracene (DMBA) at puberty accelerated spontaneous breast carcinogenesis in mouse mammary tumor virus-polyoma middle tumor-antigen transgenic (MMTV-PyMTtg or PyMT) and MMTV-Her2/neutg (Her2) mice. Paradoxically, DMBA-treated PyMT and Her2 animals were protected from metastasis. CD8+ T cells significantly infiltrated DMBA-exposed breast cancers. CD8+ T cell depletion resulted in severe lung and liver metastasis in DMBA-treated PyMT mice. Besides increasing tumor mutational burden, DMBA exposure up-regulated Chemokine (C-C motif) ligand 21 (CCL21) in cancer cells and heightened antigen presentation. CCL21 injection suppressed breast cancer growth, and CCL21 receptor deletion attenuated T cell immunity against cancer metastasis in DMBA-treated PyMT animals. CCL21 expression correlated with increased mutational burden and cytolytic activity across human cancers. Higher CCL21 levels correlated with increased CD8+ T cell infiltrates in human breast cancer and predicted lower breast cancer distant recurrence rate. Collectively, carcinogen exposure induces immune-activating factors within cancer cells that promote CD8+ T cell immunity against metastasis.

Association of the level of HER2/neu (HER2) gene amplification in breast cancer and the magnitude of antigen specific T-cell immunity achieved after HER2 vaccination

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3059-3059
Author(s):  
D. Wallace ◽  
M. Disis ◽  
A. Coveler ◽  
D. Higgins ◽  
J. Childs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
T Cell ◽  
Gene Amplification ◽  
Cell Response ◽  
T Cell Response ◽  
T Cell Immunity ◽  
Her2 Gene ◽  
Cell Immunity ◽  
Her2 Gene Amplification

3059 Background: Studies have demonstrated that the level of HER2 gene amplification in breast cancer, assessed by fluorescence in situ hybridization (FISH), correlates with favorable clinical response after treatment with trastuzumab. We questioned whether HER2 gene amplification impacted the development of HER2-specific T-cell immunity following immunization with a HER2 vaccine. Methods: Patients with HER2+ stage III or IV breast cancer, treated to complete remission or stable bone only disease, were enrolled in one of two concurrent clinical trials of HER2-specific vaccines. Eligibility criteria between the two studies were similar. Patients received either a plasmid DNA-based vaccine encoding the HER2 intracellular domain or a peptide-based vaccine composed of 3 HER2 class II epitopes. Peripheral blood was assessed for HER2-specific T-cell responses by interferon gamma (IFN-g) ELISPOT prior to, immediately after, and 6 months to 1 year after the end of vaccinations. Both immune response and FISH data were available on 31 patients. Results: Correlation of FISH levels to IFN-g spots/well in evaluable patients revealed the level of HER2 gene amplification was not related to the presence of pre-existent HER2-specific T-cell immunity prior to vaccination (p=0.43), the generation of a HER2-specific immune response after vaccination (p=0.35), or the persistence of the HER2-specific T-cell response (p=0.33). However, the magnitude of the T-cell response achieved was less as HER2 gene amplification increased (p=0.05). Conclusions: The level of HER2 gene amplification in the primary tumor can adversely impact the magnitude of HER2-specific T-cell immunity achieved after vaccination. No significant financial relationships to disclose.

scholarly journals Differences in T-cell immunity toward tumor-associated antigens in colorectal cancer and breast cancer patients

2003 ◽  
Vol 105 (2) ◽  
pp. 221-225 ◽  
Author(s):  
Dirk Nagorsen ◽  
Carmen Scheibenbogen ◽  
Gerhard Schaller ◽  
Binta Leigh ◽  
Alexander Schmittel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Colorectal Cancer ◽  
T Cell ◽  
Cancer Patients ◽  
T Cell Immunity ◽  
Breast Cancer Patients ◽  
Tumor Associated Antigens ◽  
Cell Immunity

Pre-existing T-cell immunity against mucin-1 in breast cancer patients and healthy volunteers

2005 ◽  
Vol 132 (4) ◽  
pp. 265-274 ◽  
Author(s):  
Brigitte Gückel ◽  
Christine Rentzsch ◽  
Maria-Dorothea Nastke ◽  
Alexander Marmé ◽  
Ines Gruber ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Healthy Volunteers ◽  
Cancer Patients ◽  
T Cell Immunity ◽  
Breast Cancer Patients ◽  
Mucin 1 ◽  
Cell Immunity

scholarly journals Loss of host tissue transglutaminase boosts antitumor T cell immunity by altering STAT1/STAT3 phosphorylation in ovarian cancer

2021 ◽  
Vol 9 (9) ◽  
pp. e002682
Author(s):  
Livia Elena Sima ◽  
Siqi Chen ◽  
Horacio Cardenas ◽  
Guangyuan Zhao ◽  
Yinu Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Tissue Transglutaminase ◽  
T Cell Immunity ◽  
Cell Populations ◽  
Tumor Bearing ◽  
Cell Immunity ◽  
Stat3 Phosphorylation

BackgroundTissue transglutaminase (TG2), an enzyme overexpressed in cancer cells, promotes metastasis and resistance to chemotherapy. Its distinct effects in cancer versus the host compartments have not been elucidated.MethodsHere, by using a TG2-/- syngeneic ovarian cancer mouse model, we assessed the effects of TG2 deficiency in the host tissues on antitumor immunity and tumor progression. Multicolor flow cytometry was used to phenotype immune cell populations in the peritoneal environment. Cancer cells recovered from malignant ascites were characterized by RNA sequencing, proliferation, and apoptosis assays.ResultsWe observed that host TG2 loss delayed tumor growth and ascites accumulation and caused increased infiltration of CD8+ T cells and decreased numbers of myeloid cells in the peritoneal fluid. Tumor antigen-specific CD8+ T cell cytotoxic responses were enhanced in ascites from TG2-/- versus TG2+/+ mice and CD8+ T cell depletion caused accelerated ascites accumulation in TG2-/- mice. CD8+ T cells from tumor-bearing TG2-/- mice displayed an effector T cell phenotype, differentiated toward effector memory (Tem). Mechanistically, absence of TG2 augmented signals promoting T cell activation, such as increased cytokine-induced STAT1 and attenuated STAT3 phosphorylation in T cells. Additionally, immune-suppressive myeloid cell populations were reduced in the peritoneal milieu of TG2-/- tumor-bearing mice. In response to the more robust immune response caused by loss of TG2, cancer cells growing intraperitoneally exhibited an interferon-γ(IFN-γ) responsive gene signature and underwent apoptosis. In human specimens, stromal, not tumor, TG2 expression correlated indirectly with numbers of tumor-infiltrating lymphocytes.ConclusionsCollectively, our data demonstrate decreased tumor burden, increased activation and effector function of T cells, and loss of immunosuppressive signals in the tumor microenvironment of TG2-/- mice. We propose that TG2 acts as an attenuator of antitumor T cell immunity and is a new immunomodulatory target.

scholarly journals Telomerase-Specific T-Cell Immunity in Breast Cancer: Effect of Vaccination on Tumor Immunosurveillance

2007 ◽  
Vol 67 (21) ◽  
pp. 10546-10555 ◽  
Author(s):  
Susan M. Domchek ◽  
Adri Recio ◽  
Rosemarie Mick ◽  
Carolyn E. Clark ◽  
Erica L. Carpenter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
T Cell Immunity ◽  
Tumor Immunosurveillance ◽  
Cell Immunity
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