Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
  • 2
    Abstract: Tumor-specific memory T cells are detectable in the bone marrow (BM) of a majority of breast cancer patients. In vitro they can be reactivated to IFN-gamma producing, cytotoxic effector cells and reject autologous, xenotransplanted tumors in NOD/SCID mice after specific restimulation with autologous dendritic cells (DC). In this study, we demonstrate the presence of specific tumor-reactive BM memory T cells in altogether 56 out of 129 primarily operated breast cancer patients by short-term IFN-gamma EliSpot assays with unstimulated T cells and tumor antigen presenting, autologous DCs. We observed tumor-reactive BM memory T cells predominantly in patients with primarily metastatic disease (P = 0.011) or with increased concentrations of tumor marker CA 15-3 in the peripheral blood (P = 0.004), respectively. Memory T cell reactivity against HLA-A(*0201)-restricted peptides from the tumor-associated antigens MUC1, Hpa(16-24) and Hpa(183-191) was also detected particularly in patients with elevated peripheral CA 15-3 concentrations (P 〈 0.05). Altogether these data indicate that the systemic presence of tumor-derived antigens promotes an induction of tumor-specific cellular immune responses in the human BM.
    Type of Publication: Journal article published
    PubMed ID: 19957084
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Abstract: Breast cancer and associated diabetes mellitus have gained raising interest as an elevated risk of breast cancer prognosis resulting in increased mortality in diabetic patients. In this context, the long-acting insulin analog glargine and other antidiabetics have been discussed to promote tumorigenesis. In contrast, the biguanide class oral antidiabetic metformin has been shown capable of enhancing cell cycle arrest and inducing apoptosis as well as reducing growth factor signaling. Consequently, several studies are underway to evaluate a possible role of metformin in breast cancer treatment. Although mechanisms involved are not definitely clear yet, here, we discuss metformin's anticancer effects including the potential impact of the immune system.
    Type of Publication: Journal article published
    PubMed ID: 21681370
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: IN-VIVO ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; MEMORY T-CELLS ; TGF-BETA ; MESENCHYMAL STEM-CELLS ; HORMONE-RELATED PROTEIN ; zoledronic acid ; METASTATIC BREAST-CANCER ; TARGETED THERAPY ; DORMANT TUMOR-CELLS
    Abstract: The bone marrow (BM) of cancer patients is considered an essential secondary lymphoid organ with substantial impact on tumor cell dissemination and tumor-immune responses. Recent advances in the understanding of BM/primary tumor crosstalk, homing processes, premetastatic niche formation, tumor cell dormancy, and ultimately, identification of the BM micromilieu cytokines, chemokines, and growth factors may provide the basis for the development of targeted therapeutic strategies potentially rendering primary cancers and cancer bone metastases more susceptible to chemotherapy. The present review aims to dissect the individual components of the BM microenvironment in cancer patients, compare it to the healthy BM, and discuss its impact on interactions between the tumor and the immune system.
    Type of Publication: Journal article published
    PubMed ID: 23081701
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Abstract: PURPOSE: While intact circulating tumor cells (iCTC) have independent negative prognostic impact on patients with metastatic breast cancer (MBC), the prognostic relevance of apoptotic CTC (aCTC) has not been validated in larger patient cohorts. This study assessed aCTC and iCTC statuses at baseline (CTCBL) and CTC kinetics (CTCKIN) as changes from CTCBL to one completed treatment cycle for their utility in predicting response, progression-free survival (PFS), and overall survival (OS) in MBC. METHODS: Status of iCTC and aCTC was prospectively assessed in 442 patients using the CellSearch system. Different cutoffs were analyzed both for iCTC and aCTC (〉/=5, 〉/=10, 〉/=25 and 〉/=50 CTC/7.5 ml). CTCKIN were characterized by 〉/=25 % changes in CTC counts. RESULTS: Numbers of iCTC and aCTC at baseline correlated strongly (r = 0.7). For iCTCBL positive patients, additional detection of aCTCBL had a significant prognostic impact on OS (aCTCBL positive 10.3 vs. aCTCBL negative 16.4 months, p = 0.012). Worst prognosis for OS was observed in patients with 〉/=50 iCTC/7.5 ml and simultaneously detected aCTC. Determination of aCTCKIN showed stronger discriminating power than iCTCKIN, with higher PFS and OS for the group with decreasing CTCs (PFS 7.7 vs. 6.1; OS 22.2 vs. 16.4). CONCLUSIONS: Intact and aCTC are predictive of outcome in MBC. Apoptotic CTC counts 〉/= 5/7.5 ml in conjunction with iCTC at baseline have an independent unfavorable prognostic impact on OS. Decreasing aCTCKIN at 〉/= 5/7.5 ml in serial enumeration is associated with favorable outcome. Therefore, separate enumeration of iCTC and aCTC is useful in tailoring systemic treatment.
    Type of Publication: Journal article published
    PubMed ID: 27696083
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Abstract: PURPOSE: Advances in genetics and increased public awareness increased the demand for interdisciplinary genetic outpatient consultation (IOGC). Communicating cancer risk is complex, and ideally information transfer should be individualized. Although psychological experiences with genetic testing have been studied in detail, studies on long-term experiences with IOGC and information transfer are lacking. We assessed patients' understanding and satisfaction with IOGC in families at risk of hereditary breast and ovarian cancer (HBOC) with the aim of informing best clinical practice, improving compliance and informed decision-making. METHODS: Female counselees referred for IOGC between July 1, 2009 and July 1, 2011 were eligible. Data were collected using a 47-item postal questionnaire to assess sociodemographic, psychological, behavioral parameters. Overall satisfaction and personal usefulness of IOGC were assessed with a five-point, and risk perception with a visual analog scale. Data were analyzed using Spearman rank, Wilcoxon U or Chi-squared test. RESULTS: 612 (72 %) of 849 women participated reported being highly satisfied (75 %, n = 430) and declared personal usefulness (73 %, n = 421) on average 3.5 years after IOGC. Women deemed "high risk" assessed their risk of developing BC as significantly higher than non-high-risk counselees (3.2 versus 3.0, p = 0.00484). Risk perception was lower in BRCA1/2 mutation carriers than in women with unclassified variants or no mutation (2.8 versus 3.5 and 3.1, respectively). CONCLUSION: Women with an HBOC background have additional needs to achieve long-term satisfaction after IOGC. Prospective studies are required to optimize care for the increasing number of people who seek genetic consultation, particularly as the complexity of genetics knowledge increases.
    Type of Publication: Journal article published
    PubMed ID: 27282618
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Keywords: CANCER ; tumor ; FOLLOW-UP ; RISK ; TIME ; INFECTION ; breast cancer ; MICROMETASTASES ; PROGNOSTIC-SIGNIFICANCE ; body mass index ; PAIN ; ISOLATED TUMOR-CELLS ; ASPIRATION ; BIOPSY MORBIDITY ; Bone marrow puncture ; DTCs ; PRIMARY SURGERY ; Side-effects
    Abstract: BACKGROUND AND AIM: In breast cancer patients, intraoperative bone marrow puncture (BMP) with positive detection of disseminated tumor cells has been reported to predict unfavorable clinical outcome due to increased risk of recurrence. In this study, we prospectively assessed BMP-associated untoward side-effects. METHODS: Fifty-eight consecutive breast cancer patients were prospectively explored after intraoperative BMP for postoperative pain (visual analogue scale, VAS) and complications in terms of infection, hematoma, and sensibility disorder. Furthermore, the impact of BMP on hospital stay duration was analyzed in 254 patients. RESULTS: In all subgroups analyzed, during five postoperative days patients complained about minor pain only at the site of BMP (VAS 〈 1) while the corresponding pain scores were significantly higher for the area of the operated breast. Post-BMP iliac crest hematomas were encountered in 13 out of 58 patients (22.4%) who were significantly older (p = 0.04), less frequently smokers (p = 0.02), and presented with higher body mass index (p = 0.01) than controls. Within the area of BMP no signs of infection or sensibility disorders were observed. Comparison of patients with and without BMP did not show any significant difference in postoperative hospital stay duration. CONCLUSION: Referring to the potential clinical benefit of intraoperative BMP its prospectively assessed adverse side-effects appear relatively mild and thus acceptable.
    Type of Publication: Journal article published
    PubMed ID: 20621481
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Keywords: CANCER ; EXPRESSION ; IN-VIVO ; GENERATION ; DISEASE ; SITE ; TISSUE ; RESPONSES ; SKIN ; ASSOCIATION ; bone marrow ; BONE-MARROW ; breast cancer ; LYMPHOCYTES ; IMMUNITY ; INTERFERON-ALPHA ; AUTOIMMUNITY ; DISORDERS ; LUPUS-ERYTHEMATOSUS ; REACTIVE T-CELLS ; TUMOR BIOLOGY ; anti-tumor ; T-cell immunity
    Abstract: A wide variety of cancer types has been associated with paraneoplastic autoimmune disorders and with the induction of autoimmunity against several autoantigens, among them self-antigens that are also expressed by tumor cells. This raises the question of autoimmune disorders as a result of immune reactions to the tumor. To date, however, requirements for the generation of autoimmune reactions in cancer patients remain largely unclear. In this study, we characterized conditions in altogether 131 patients, which determine autoimmune responses in primary breast cancer patients. We used ex vivo IFN-gamma EliSpot assays against autologous tumor or skin lysates to evaluate tumor- and auto-reactive T-cells (TCs) in the bone marrow (BM) as well as ELISA, ECLIA, and turbidimetric immunoassays for the detection of auto-reactive antibodies in the peripheral blood and compared results to intratumoral cytokine concentrations and pathobiological features of the primary tumor tissue. We here demonstrate a significant correlation between anti-tumor BMTC responses and cellular autoimmune reactivity in primary breast cancer patients (P = 0.002). Humoral autoimmune reactions, however, were negatively correlated with anti-tumor TC immunity (P = 0.039). We observed auto-reactive BMTCs especially in patients with well-differentiated, hormone receptor-positive carcinomas (P = 0.009). Furthermore, elevated concentrations of intratumoral IFN-alpha significantly correlated with the induction of cellular autoimmune reactivity (P = 0.0002), while humoral autoimmune reactions correlated with increased levels of intratumoral IL-12 (P = 0.04). Altogether, these data indicate a significant role of the tumor microenvironment and particularly that of IFN-alpha and IL-12 in the induction of systemic autoimmune responses and imply that the primary tumor tissue represents an integral site of autoimmune regulation in cancer patients
    Type of Publication: Journal article published
    PubMed ID: 21161218
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: IN-VITRO ; carcinoma ; ANTITUMOR-ACTIVITY ; BONE-MARROW ; breast cancer ; OVARIAN-CANCER ; METASTATIC MELANOMA ; AUTOIMMUNITY ; REGULATORY T-CELLS ; regulatory T cells ; TUMOR-IMMUNITY ; tumor-specific T cells ; immunomodulation ; LOW-DOSE CYCLOPHOSPHAMIDE
    Abstract: Severe immune suppression is frequent in late-stage tumor patients and promotes tumor immune evasion and subsequent tumor progression. Regulatory T cells (Treg) are major suppressors of anti-tumor immune responses. Therefore, targeting of Treg has become a key goal of anti-tumor therapy. Several preclinical and clinical observations suggest that Treg can be depleted by cyclophosphamide. Over a period of 3 months, we investigated the effect of metronomic low-dose cyclophosphamide on Treg numbers, suppressive capacity and proliferation on endogenous anti-tumor T-cell responses and on their correlation to clinical outcome in 12 patients with treatment-refractory metastasized breast cancer who received single-agent 50 mg cyclophosphamide p.o. daily. Cyclophosphamide treatment initially caused a significant reduction in circulating Treg by more than 40% (P = 0.002). However, Treg numbers completely recovered during the treatment due to increased proliferative activity and maintained their suppressive capacity. Treg depletion coincided with a strong increase in breast tumor-reactive T cells (P = 0.03) that remained at high levels during the whole period. Numbers of tumor-reactive T cells but not of Treg correlated with disease stabilization (P = 0.03) and overall survival (P = 0.027). We conclude that metronomic low-dose cyclophosphamide only transiently reduces Treg but induces stable tumor-specific T-cell responses, which correlate with improved clinical outcome in advanced-stage breast cancer patients.
    Type of Publication: Journal article published
    PubMed ID: 21915801
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Keywords: carcinoma ; DIFFERENTIATION ; RESPONSES ; LYMPHOCYTES ; CD8(+) ; ANTITUMOR IMMUNITY ; INFILTRATION ; METASTATIC MELANOMA PATIENTS ; EFFECTOR FUNCTIONS ; CENTRAL MEMORY
    Abstract: BACKGROUND: The bone marrow (BM) of breast cancer patients harbors tumor-reactive memory T cells (TCs) with therapeutic potential. We recently described the immunologic effects of adoptive transfer of ex vivo restimulated tumor-reactive memory TCs from the BM of 12 metastasized breast cancer patients in a clinical phase-I study. In this trial, adoptive T cell transfer resulted in the occurrence of circulating tumor antigen-reactive type-1 TCs. We here describe the long-term clinical outcome and its correlation with tumor-specific cellular immune response in 16 metastasized breast cancer patients, including 12 included in the original study. METHODS: Sixteen metastatic breast cancer patients with preexisting tumor-reactive BM memory TCs were included into the study. The study protocol involved one transfusion of TCs which were reactivated in vitro with autologous dendritic cells pulsed with lysates of MCF-7 breast cancer cells as source of tumor antigens. The presence of tumor-reactive memory TCs was analyzed by IFN-gamma ELISpot assays. RESULTS: Tumor-reactive memory TCs in the peripheral blood were induced de novo in 7/16 patients (44 %) after adoptive TC transfer. These patients were considered immunologic responders to the therapy. Positive adoptive immunotherapy (ADI) response was observed significantly more often in patients without bone metastases (p = 0.0051), in patients with high levels of tumor-reactive BM TCs prior to therapy (p = 0.036) and correlated significantly with the estimated numbers of transferred tumor-reactive TCs (p = 0.0021). After the treatment, we observed an overall median survival of 33.8 months in the total cohort with three patients alive at last follow-up and more than 7 years after ADI. Numbers of transferred tumor-reactive TCs correlated significantly with the overall survival of patients (p = 0.017). Patients with an immunologic response to ADI in the peripheral blood had a significantly longer median survival than nonresponders (median survival 58.6 vs. 13.6 months; p = 0.009). CONCLUSION: In metastasized breast cancer patients, adoptive transfer of BM TCs can induce the presence of tumor antigen-reactive type-1 TCs in the peripheral blood. Patients with immunologic response after ADI show a significantly longer overall survival. Patients with bone metastases significantly less frequently respond to the treatment and, therefore, might not be optimal candidates for ADI. Although the present study does not yet prove the therapeutic effect of ADI, these findings shed light on the relation between immune response and cancer prognosis and suggest that transfer of reactivated BM TCs might bear therapeutic potential.
    Type of Publication: Journal article published
    PubMed ID: 23595207
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...