MHC class I negative phenotype of disseminated tumor cells in bone marrow is associated with poor survival in R0M0 breast cancer patients

Zia, Ahmad; Schildberg, F. W.; Funke, I.

doi:10.1002/ijc.1362

Cited by 35 publications

(22 citation statements)

References 19 publications

(19 reference statements)

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“…Further, NKCA was an independent prognostic factor for overall survival in that study (Liljefors et al, 2003). It is worth noting that breast cancer cells can express relatively little or no HLA (Redondo, et al, 2003;Zia, et al, 2001). This is a particularly important observation with relevance to breast cancer in that "recognition" of missing HLA is one means by which NK cells destroy tumor cells.…”

Section: Discussionmentioning

confidence: 74%

Effect of mindfulness based stress reduction on immune function, quality of life and coping in women newly diagnosed with early stage breast cancer

Witek-Janusek

Albuquerque

Chroniak

et al. 2008

Brain, Behavior, and Immunity

394

324

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This investigation used a non-randomized controlled design to evaluate the effect and feasibility of a mindfulness based stress reduction (MBSR) program on immune function, quality of life (QOL), and coping in women recently diagnosed with breast cancer. Early stage breast cancer patients, who did not receive chemotherapy, self-selected into an 8-week MBSR program or into an assessment only, control group. Outcomes were evaluated over time. The first assessment was at least 10 days after surgery and prior to adjuvant therapy, as well as before the MBSR start-up. Further assessments were mid-MBSR, at completion of MBSR, and at 4-weeks post MBSR completion. Women with breast cancer enrolled in the control group (Non-MBSR) were assessed at similar times. At the first assessment (i.e., before MBSR start), reductions in peripheral blood mononuclear cell NK cell activity (NKCA) and IFN gamma production with increases in IL-4, IL-6, and IL-10 production and plasma cortisol levels were observed for both the MBSR and Non-MBSR groups of breast cancer patients. Over time women in the MBSR group re-established their NKCA and cytokine production levels. In contrast, breast cancer patients in the Non-MBSR group exhibited continued reductions in NKCA and IFN gamma production with increased IL-4, IL-6, and IL-10 production. Moreover, women enrolled in the MBSR program had reduced cortisol levels, improved QOL, and increased coping effectiveness compared to the Non-MBSR group. In summary, MBSR is a program that is feasible for women recently diagnosed with early stage breast cancer and the results provide preliminary evidence of beneficial effects of MBSR on immune function, QOL, and coping effectiveness.

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Section: Discussionmentioning

confidence: 74%

Effect of mindfulness based stress reduction on immune function, quality of life and coping in women newly diagnosed with early stage breast cancer

Witek-Janusek

Albuquerque

Chroniak

et al. 2008

Brain, Behavior, and Immunity

394

324

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“…Thus in theory, breast cancer cells expressing little or no MHC class I might escape recognition by MHC-restricted CD8+ CTL. Indeed, it has been proposed that reduced expression of MHC class I on breast cancer cells may be associated with poorer clinical outcomes [17][18][19]. Such findings underscore the need to develop cellular immunotherapy strategies which do not utilize classical MHC-restricted antigen processing and presentation in the recognition and elimination of tumor cells.…”

Section: Introductionmentioning

confidence: 98%

Innate Anti-breast Cancer Immunity of Apoptosis-resistant Human γδ-T cells

Guo

Aldrich

et al. 2005

Breast Cancer Res Treat

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We previously identified a CD2-initiated signaling pathway which inhibits activation-induced cell death in mitogen-stimulated human gammadelta-T cells permitting the large-scale expansion of these cells. Here we report the innate anti-tumor activity of expanded human gammadelta-T cells against human breast cancer cells. Apoptosis-resistant human gammadelta-T cells which were expanded in vitro from cultured human peripheral blood mononuclear cells displayed lytic activity against breast cancer cell lines MDA-MB-231, MCF-7 and T-47D, but failed to kill normal human skin fibroblasts and normal human liver cells. Monoclonal antibodies (mAb) directed against the gammadelta-T cell receptor (TCR) or mAb directed against either the Vgamma9 or the Vdelta2 TCR chains were able to block gammadelta-T cell-mediated lysis of MDA-MB-231 cells. In addition, mAb against intercellular adhesion molecules-1 (ICAM-1/CD54) or CD18 (beta subunit of ICAM-1 counter-receptor) also blocked gammadelta-T cell-mediated killing of MDA-MB-231 cells. Ex vivo expanded human gammadelta-T cells are thus able to innately recognize and kill human breast cancer cells in a gammadelta-TCR-dependent manner; ICAM-1 and CD18 also appear to be involved in the interactions between sensitive breast cancer cells and cytolytic gammadelta-T cells. As apoptosis-resistant human gammadelta-T cells can now readily be expanded to large numbers (clinical scale), these findings must be considered in the context of developing adoptive immunotherapy strategies to exploit gammadelta-T cell innate immune responses for the primary or adjuvant treatment of breast cancer.

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“…R educed expression of HLA class I on tumors is often associated with disease progression and poor prognosis in diverse human tumors, including ovarian, colorectal, and breast cancer (1)(2)(3). We demonstrated previously that downregulation of HLA class I molecules occurred in 43% of the primary tumors in patients with esophageal squamous cell carcinoma (ESCC) and was associated with a poor prognosis (4).…”

mentioning

confidence: 99%

The MAPK Pathway Is a Predominant Regulator of HLA-A Expression in Esophageal and Gastric Cancer

Mimura

Shiraishi

Müeller

et al. 2013

The Journal of Immunology

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Downregulation of HLA class I expression may contribute to a poor prognosis in cancer patients. There is limited information about epigenetic and oncogenic regulation of HLA class I, and multiple mechanisms may be involved. In the current study, we examined the relationship between the HER2-signaling pathway (MAPK and PI3K-Akt) and the expression of HLA class I and Ag-processing machinery (APM) components. A panel of gastric and esophageal cancer cell lines was treated with wortmannin as an Akt-signal inhibitor; the MAPK signal inhibitor PD98059; lapatinib, which inhibits both the epidermal growth factor receptor and HER2 tyrosine kinase; or siRNA for MAPK. The levels of HER2-signaling molecules, APM components, and HLA class I were evaluated by Western blot, quantitative PCR, and flow cytometry. Resected gastric tumor tissues (n = 102) were analyzed for p-Erk and HLA class I expression by immunohistochemistry. As a result, inhibition of the MAPK pathway induced upregulation of HLA-A02 and HLA-A24 expression in parallel with an increase in APM components and enhanced target sensitivity to tumor Ag–specific CTL lysis. HLA-A expression was predominantly regulated by the MAPK pathway, but it was also influenced, in part, by the Akt pathway. There was a strong inverse correlation between p-Erk expression and HLA class I expression in clinical tumor samples. In conclusion, HLA-A expression is predominantly regulated by the MAPK pathway in gastric and esophageal cancer.

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MHC class I negative phenotype of disseminated tumor cells in bone marrow is associated with poor survival in R0M0 breast cancer patients

Cited by 35 publications

References 19 publications

Effect of mindfulness based stress reduction on immune function, quality of life and coping in women newly diagnosed with early stage breast cancer

Effect of mindfulness based stress reduction on immune function, quality of life and coping in women newly diagnosed with early stage breast cancer

Innate Anti-breast Cancer Immunity of Apoptosis-resistant Human γδ-T cells

The MAPK Pathway Is a Predominant Regulator of HLA-A Expression in Esophageal and Gastric Cancer

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