Macrophage infiltrate and prognosis in c-erbB-2-overexpressing breast carcinomas.

Pupa, Serenella M.; Bufalino, Rosaria; Invernizzi, Annamaria; Andreola, Salvatore; Rilke, F; Lombardi, Luciano; Colnaghi, Maria I.; Ménard, Sylvie

doi:10.1200/jco.1996.14.1.85

Cited by 64 publications

(42 citation statements)

References 26 publications

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“…Several studies have previously established that patients with tumors overexpressing the ErbB2 protein, can spontaneously develop natural immunity to this receptor in the apparent absence of structural abnormalities (Pupa et al, 1993;Disis et al, 1994aDisis et al, ,b, 1997Fisk et al, 1995;Peoples et al, 1995;Clark et al, 1997). In the present study, we extend this observation by demonstrating the presence of speci®c antibody responses against all ErbB receptors including EGFR, ErbB2, ErbB3 and ErbB4 in tumor patients with di erent epithelial malignancies.…”

Section: Discussionsupporting

confidence: 77%

“…Humoral responses directed against the EGFR have been reported (Glushkov et al, 1996). Moreover, it has been reproducibly documented that some breast and ovarian tumor patients mount natural T and B cell responses to ErbB2 (Pupa et al, 1993;Disis et al, 1994aDisis et al, ,b, 1997Fisk et al, 1995;Peoples et al, 1995;Clark et al, 1997). This receptor has triggered particular interest based upon evidence that its overexpression independently predicts a worse disease course in lymph node positive breast cancer (Slamon et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

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Immune responses to all ErbB family receptors detectable in serum of cancer patients

et al. 1999

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Employing NIH3T3 transfectants with individual human ErbB receptor coding sequences as recombinant antigen sources, we detected by immunoblot analysis speci®c immunoreactivity against all four ErbB receptors among 13 of 41 sera obtained from patients with di erent types of epithelial malignancies. Overall, serum positivity was most frequently directed against ErbB2 followed by EGFR, ErbB3 and ErbB4. Speci®city patterns comprised tumor patients with unique serum reactivity against ErbB2 or ErbB4. Moreover, approximately half of the positive sera exhibited concomitant reactivity with multiple ErbB receptors including EGFR and ErbB2, EGFR and ErbB4, ErbB2 and ErbB3 or EGFR, ErbB2 and ErbB3. Serum reactivity was con®rmed for the respective ErbB receptors expressed by human tumor cells and corroborated on receptor-speci®c immunoprecipitates. Positive sera contained ErbB-speci®c antibodies of the IgG isotype. Representative immunohistochemical analysis of tumor tissues suggested overexpression of ErbB receptors for which serum antibodies were detectable in ®ve of six patients. These ®ndings implicate multiple ErbB receptors including ErbB3 and ErbB4 in addition to EGFR and ErbB2 in primary human cancer. Heterogeneity of natural ErbB-speci®c responses in cancer patients warrants their evaluation in light of immunotherapeutic approaches targeting these receptors.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Immune responses to all ErbB family receptors detectable in serum of cancer patients

et al. 1999

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“…It may be that macrophages and fibroblasts have an important role in the early steps of tumour pathogenesis by inhibiting both angiogenesis and other mechanisms involved in the metastatic process. This hypothesis is supported by a recent study in breast cancer (Pupa et al, 1996), in which macrophage infiltration, although related to better prognosis, was also correlated with C-erbB-2 positivity. C-erbB-2 protein is well known to disrupt cell adhesion and to confer migratory abilities on cancer cells (Kanai et al, 1995).…”

Section: Discussionsupporting

confidence: 68%

Different patterns of stromal and cancer cell thymidine phosphorylase reactivity in non-small-cell lung cancer: impact on tumour neoangiogenesis and survival

Koukourakis

Giatromanolaki²,

Kakolyris³

et al. 1998

Br J Cancer

113

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Summary Angiogenesis is recognized as an important step in tumour pathogenesis that is related to invasion and metastatic spread and which consequently results in poor clinical outcome. In this study, we have examined the role of tumour stroma-activated fibroblasts and macrophage infiltration in the development of the angiogenic and metastatic phenotype in non-small-cell lung cancer (NSCLC). A total of 141 cases of early stage I-Il NSCLC treated with surgery alone were analysed. The JC-70 (anti-CD31) MAb was used for the assessment of vascular grade. The P-GF.44C MAb was used to assess thymidine phosphorylase (TP) reactivity in cancer cells, stromal fibroblasts and macrophages. Cancer cell TP overexpression related to high vascular grade and to advanced T stage (P = 0.0004 and P = 0.02). Expression of TP in stromal fibroblasts also correlated with high angiogenesis (P = 0.01), but was independent of cancer cell expression. Fibroblast TP overexpression was related to abundant stroma (P = 0.003), suggesting that TP may be a marker of active stroma. Moreover, intense macrophage infiltration was associated with fibroblast TP reactivity, regardless of the amount of stroma, suggesting that macrophages may be a major contributor to TP expression in stroma. Survival analysis showed that cancer cell TP overexpression was related to poor prognosis (P = 0.005). Although stroma TP is related to angiogenesis, in the low vascular grade group it defined a group of patients with better prognosis (P = 0.02). It may be that fibroblast TP reactivity is an indirect marker of tumour infiltration by functional macrophages, which have an antitumour effect. We conclude that stromal macrophage and fibroblast TP reactivity may have an important role in non-small-cell lung cancer behaviour. Understanding the role of stromal fibroblasts and inflammatory cells and their interaction with oncoprotein expression is essential for the elucidation of lung cancer pathogenesis.

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“…Although HER2 is generally indicative of a poor prognosis, its overexpression is associated with a better outcome when inflammatory infiltrates are present in the tumor, suggesting a role for HER2 in tumor immunosurveillance (Rilke et al, 1991;Me´nard et al, 1996;Pupa et al, 1996). In keeping, development of HER2-specific antibodies has been documented in patients with primary HER2-positive tumors (Pupa et al, 1993;Disis et al, 1994Disis et al, , 1997b, and T cells reactive to HER2 were found to occur in patients with HER2-positive tumors (Disis and Cheever, 1997a), confirming the immunogenicity of the molecule.…”

Section: Her2 As a Target For Therapymentioning

confidence: 99%

Biologic and therapeutic role of HER2 in cancer

et al. 2003

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Macrophage infiltrate and prognosis in c-erbB-2-overexpressing breast carcinomas.

Abstract: Our data demonstrate different leukocytic types in the infiltrate of breast tumors with different prognostic significance.

Cited by 64 publications

References 26 publications

Immune responses to all ErbB family receptors detectable in serum of cancer patients

Immune responses to all ErbB family receptors detectable in serum of cancer patients

Different patterns of stromal and cancer cell thymidine phosphorylase reactivity in non-small-cell lung cancer: impact on tumour neoangiogenesis and survival

Biologic and therapeutic role of HER2 in cancer

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