Determination of paraneoplastic autoimmune responses by tumor cell biology and intratumoral IFN-alpha/IL-12 in breast cancer patients

被引：3

作者：

Domschke, Christoph ^{[1
]}

Schuetz, Florian ^{[1
]}

Ge, Yingzi ^{[4
]}

Rom, Joachim ^{[1
]}

Zorn, Markus ^{[2
]}

Sinn, Hans-Peter ^{[3
]}

Marme, Frederik ^{[1
]}

Schott, Sarah ^{[1
]}

Heil, Joerg ^{[1
]}

Scharf, Alexander ^{[1
]}

Sohn, Christof ^{[1
]}

Schneeweiss, Andreas ^{[1
]}

Beckhove, Philipp ^{[4
]}

机构：

[1] Univ Heidelberg Hosp, Dept Gynecol & Obstet, D-69115 Heidelberg, Germany

[2] Univ Heidelberg Hosp, Dept Endocrinol & Clin Chem, D-69120 Heidelberg, Germany

[3] Univ Heidelberg Hosp, Dept Pathol, D-69115 Heidelberg, Germany

[4] German Canc Res Ctr, Tumor Immunol Program, Div Translat Immunol, D-69120 Heidelberg, Germany

来源：

CANCER IMMUNOLOGY IMMUNOTHERAPY | 2011年 / 60卷 / 03期

关键词：

Breast cancer; Autoimmunity; Tumor biology; Bone marrow; T-cell immunity; REACTIVE T-CELLS; BONE-MARROW; INTERFERON-ALPHA; LUPUS-ERYTHEMATOSUS; IN-VIVO; EXPRESSION; DISORDERS; ASSOCIATION; LYMPHOCYTES; DISEASE;

D O I：

10.1007/s00262-010-0956-4

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：401 / 411

页数：11