PBLs of Early Breast Carcinoma Patients with a High Nuclear Grade Tumor Unlike PBLs of Cervical Carcinoma Patients Do Not Show a Decreased TCRξ Expression but Are Functionally Impaired

Nieland, John D.; Loviscek, K; Kono, Koji; Albain, KS; McCall, Anne R.; Potkul, Ronald K.; Fisher, S G; Velders, Markwin P.; Petersson, Max; Kiessling, Rolf; Kast, W. Martin

doi:10.1097/00002371-199807000-00009

Cited by 18 publications

(5 citation statements)

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“…The downregulation of chains in T cells is not limited to TIL, but can also be measured in peripheral blood lymphocytes (PBL) and natural killer (NK) cells of tumor-bearing patients (97,98). Studies on expression in PBL of patients with cervical intraepithelial neoplasia or cervical cancer (34) and Hodgkin's disease (35) have indicated that the chain expression may correlate with disease progression, but this hypothesis could not be confirmed in the analysis of PBL from patients with breast cancer at early stages of their disease (99). A correlation between the expression of the chain in the TIL of patients with head and neck carcinoma and their overall survival has been described (36).…”

Section: T-cell Receptor Zeta Chain Analysismentioning

confidence: 99%

Immunologic Monitoring of Cancer Vaccine Therapy: Results of a Workshop Sponsored by the Society for Biological Therapy

Keilholz¹,

Weber²,

Finke³

et al. 2002

Journal of Immunotherapy

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274

182

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The Society for Biological Therapy held a Workshop last fall devoted to immune monitoring for cancer immunotherapy trials. Participants included members of the academic and pharmaceutical communities as well as the National Cancer Institute and the Food and Drug Administration. Discussion focused on the relative merits and appropriate use of various immune monitoring tools. Six breakout groups dealt with assays of T-cell function, serologic and proliferation assays to assess B cell and T helper cell activity, and enzyme-linked immunospot assay, tetramer, cytokine flow cytometry, and reverse transcription polymerase chain reaction assays of T-cell immunity. General conclusions included: (1) future vaccine studies should be designed to determine whether T-cell dysfunction (tumor-specific and nonspecific) correlated with clinical outcome; (2) tetramer-based assays yield quantitative but not functional data (3) enzyme-linked immunospot assays have the lowest limit of detection (4) cytokine flow cytometry have a higher limit of detection than enzyme-linked immunospot assay, but offer the advantages of speed and the ability to identify subsets of reactive cells; (5) antibody tests are simple and accurate and should be incorporated to a greater extent in monitoring plans; (6) proliferation assays are imprecise and should not be emphasized in future studies; (7) the reverse transcription polymerase chain reaction assay is a promising research approach that is not ready for widespread application; and (8)there is a critical need to validate these assays as surrogates for vaccine potency and clinical effect. Current data and opinion support the use of a functional assay like the enzyme-linked immunospot assay or cytokine flow cytometry in combination with a quantitative assay like tetramers for immune monitoring. At present, assays appear to be most useful as measures of vaccine potency. Careful immune monitoring in association with larger scale clinical trials ultimately may enable the correlation of monitoring results with clinical benefit.

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Section: T-cell Receptor Zeta Chain Analysismentioning

confidence: 99%

Immunologic Monitoring of Cancer Vaccine Therapy: Results of a Workshop Sponsored by the Society for Biological Therapy

Keilholz¹,

Weber²,

Finke³

et al. 2002

Journal of Immunotherapy

Self Cite

274

182

View full text Add to dashboard Cite

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“…The few publications regarding ζ‐chain expression in breast cancer include few patients and report divergent results. While two studies observed ζ‐chain down‐regulation in only 2 of 12,34 and 4 of 14 included breast cancer patients,15 a recent study found a decreased ζ‐chain expression in 61 breast cancer patients compared with healthy controls 31. However, the latter could not find any correlation with tumor or nodal stage.…”

Section: Discussionmentioning

confidence: 95%

Rhabdomyosarcoma in adolescents

Bisogno

Compostella

Ferrari³

et al. 2011

Cancer

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BACKGROUND: In many types of cancer, the survival rates are reported to be less favorable for adolescents compared with younger children. To investigate whether this is true for adolescents with rhabdomyosarcoma (RMS), the results obtained in patients enrolled in protocols run by the Italian Soft Tissue Sarcoma Committee (STSC) were analyzed. METHODS: From 1988 through 2005, 643 patients were registered (567 children ages birth-14 years and 76 adolescents ages 15-19 years) and treated in 4 STSC protocols. The number of patients enrolled was compared with the expected number calculated from incidence rates derived from the Italian network of cancer registries. RESULTS: Only 27% of the expected number of adolescents with RMS were enrolled in the STSC trials. Compared with children, adolescents were found to have a longer interval from initial symptoms to diagnosis (8 weeks vs 4.6 weeks), more alveolar RMS (47.4% vs 32.6%), lymph node infiltration (39.1% vs 23.3%), and metastases at the time of diagnosis (30.7% vs 17.8%). The 2 age groups received similar treatments. The 5-year overall survival (OS) rate was 68.9% in children versus 57.2% in adolescents (P ¼ .006), and the progression-free survival (PFS) rate was 64.3% in children versus 48.1% in adolescents (P ¼ .0237). On multivariate analysis, age, tumor site, lymph node involvement, and metastases were found to be significant prognostic factors for OS and PFS. CONCLUSIONS: Survival for adolescents with RMS enrolled in STSC protocols appears to be satisfactory. The higher prevalence of unfavorable tumor characteristics noted among adolescents seems to explain their worse outcome compared with children. However, the limited number of adolescents enrolled in STSC studies is worrisome, and cooperation with oncologists who treat adults needs to be improved. Cancer 2012;118:821-

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“…30,31 (ii) Even in a therapeutic setting, the immune system in mice is not persistently confronted with the suppressive effects of virus-transformed cells. 32,33 Whereas in mice, due to the injection of the tumor cells, the immune system is alerted by a local inflammatory response, in humans the slow development of the lesion does not exert this effect. (iii) Transplantable murine tumors are selected for good MHC class I expression and thus are very sensitive to a HPV-specific CTL response, while in humans several escape mechanisms of the transformed cells are described, e.g., selective down-regulation of MHC expression and interference with cell signalling and cytokine production.…”

Section: Discussionmentioning

confidence: 99%

Vaccination trial with HPV16 L1E7 chimeric virus‐like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3)

Kaufmann

Nieland

Jochmus

et al. 2007

Intl Journal of Cancer

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115

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Persistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. Vaccination with virus-like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential. HPV16 L1E7 chimeric viruslike particles (CVLP) consist of a carboxy-terminally truncated HPV16L1 protein fused to the amino-terminal part of the HPV16 E7 protein and self-assemble by recombinant expression of the fusion protein. The CVLP are able to induce L1-and E7-specific cytotoxic T lymphocytes. We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans. A randomized, double blind, placebo-controlled clinical trial has been conducted in 39 HPV16 mono-infected high grade cervical intraepithelial neoplasia (CIN) patients (CIN 2/3). Two doses (75 lg or 250 lg) of CVLP were applied. The duration of the study was 24 weeks with 2 optional visits after another 12 and 24 weeks. The vaccine showed a very good safety profile with only minor adverse events attributable to the immunization. Antibodies with high titers against HPV16 L1 and low titers against HPV16 E7 as well as cellular immune responses against both proteins were induced. Responses were equivalent for both vaccine concentrations. A trend for histological improvement to CIN 1 or normal was seen in 39% of the patients receiving the vaccine and only 25% of the placebo recipients. Fifty-six percent of the responders were also HPV16 DNA-negative by the end of the study. Therefore, we demonstrated evidence for safety and a nonsignificant trend for the clinical efficacy of the HPV16 L1E7 CVLP vaccine. ' 2007 Wiley-Liss, Inc.Key words: cervical cancer; clinical trial; immunization; antibody; T cell Genital infection with human papillomavirus (HPV) is one of the most common sexually transmitted diseases. Various molecular and epidemiological studies have documented a correlation between infection with ''high risk'' HPV types and premalignant or malignant tumors of the anogenital tract. 1,2 It is widely acknowledged that a causal relationship exists between persistent HPV infection and development of cervical intraepithelial neoplasia (CIN) and cervical cancer. 3,4 There are over 100 known papillomavirus types that are stratified into low and high risk, based on their association with malignant and invasive lesions. More than 95% of invasive cervical cancers are positive for HPV-DNA, mainly from HPV types 16 (50%) and 18 (20%). Moreover, HPV16 can be detected in 30270% of all HPV-positive high grade CIN patients. 5,6 The prevalence of HPV16 in other intraepithelial neoplasias is even higher, e.g., 70280% in high grade vulvar intraepithelial neoplasia. 7 Whereas for low grade CIN a high spontaneous recovery rate is observed 6,8 high grade CIN regress less often particular at higher age when lesions are more persistent. 9 Because of the potential progression of high grade CIN to invasive cancer, 10 a thorough evaluation consisting of colp...

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PBLs of Early Breast Carcinoma Patients with a High Nuclear Grade Tumor Unlike PBLs of Cervical Carcinoma Patients Do Not Show a Decreased TCRξ Expression but Are Functionally Impaired

Cited by 18 publications

References 0 publications

Immunologic Monitoring of Cancer Vaccine Therapy: Results of a Workshop Sponsored by the Society for Biological Therapy

Immunologic Monitoring of Cancer Vaccine Therapy: Results of a Workshop Sponsored by the Society for Biological Therapy

Rhabdomyosarcoma in adolescents

Vaccination trial with HPV16 L1E7 chimeric virus‐like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3)

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