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Antibody responses to NY-ESO-1 in primary breast cancer identify a subtype target for immunotherapy.

Hamaï A, Duperrier-Amouriaux K, Pignon P, Raimbaud I, Memeo L, Colarossi C, Canzonieri V, Perin T, Classe JM, Campone M, Jézéquel P, Campion L, Ayyoub M, Valmori D - PLoS ONE (2011)

Bottom Line: We found detectable Ab responses to ESO in 1% of the patients.In line with these results, we detected ESO expression in 20% of primary HR⁻ BC, including both ESO Ab⁺ and Ab⁻ patients, but not in HR⁺ BC.Interestingly, whereas expression levels in ESO⁺ BC were not significantly different between ESO Ab⁺ and Ab⁻ patients, the former had, in average, significantly higher numbers of tumor-infiltrated lymph nodes, indicating that lymph node invasion may be required for the development of spontaneous anti-tumor immune responses.

View Article: PubMed Central - PubMed

Affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 892, CLCC René Gauducheau, Saint Herblain, France.

ABSTRACT
The highly immunogenic human tumor antigen NY-ESO-1 (ESO) is a target of choice for anti-cancer immune therapy. In this study, we assessed spontaneous antibody (Ab) responses to ESO in a large cohort of patients with primary breast cancer (BC) and addressed the correlation between the presence of anti-ESO Ab, the expression of ESO in the tumors and their characteristics. We found detectable Ab responses to ESO in 1% of the patients. Tumors from patients with circulating Ab to ESO exhibited common characteristics, being mainly hormone receptor (HR)⁻ invasive ductal carcinomas of high grade, including both HER2⁻ and HER2⁺ tumors. In line with these results, we detected ESO expression in 20% of primary HR⁻ BC, including both ESO Ab⁺ and Ab⁻ patients, but not in HR⁺ BC. Interestingly, whereas expression levels in ESO⁺ BC were not significantly different between ESO Ab⁺ and Ab⁻ patients, the former had, in average, significantly higher numbers of tumor-infiltrated lymph nodes, indicating that lymph node invasion may be required for the development of spontaneous anti-tumor immune responses. Thus, the presence of ESO Ab identifies a tumor subtype of HR⁻ (HER2⁻ or HER2⁺) primary BC with frequent ESO expression and, together with the assessment of antigen expression in the tumor, may be instrumental for the selection of patients for whom ESO-based immunotherapy may complement standard therapy.

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Assessment of ESO expression in ER− and ER+ BC tumors.A and B. ESO expression in cryopreserved ER− and ER+ BC tumors was assessed by semi-quantitative PCR (A) and qPCR (B). C. The level of ESO expression in the tumor as assessed by qPCR (left panel, mean ± SD), the size of the primary tumor at diagnosis (middle panel, mean ± SD) and the number of tumor-invaded lymph nodes (right panel, mean ± SD) are shown for ESO Ab+ (n = 8) and ESO Ab− (n = 10) patients with ESO-expressing tumors. Statistical analyses were performed using a two-tailed t-test.
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pone-0021129-g003: Assessment of ESO expression in ER− and ER+ BC tumors.A and B. ESO expression in cryopreserved ER− and ER+ BC tumors was assessed by semi-quantitative PCR (A) and qPCR (B). C. The level of ESO expression in the tumor as assessed by qPCR (left panel, mean ± SD), the size of the primary tumor at diagnosis (middle panel, mean ± SD) and the number of tumor-invaded lymph nodes (right panel, mean ± SD) are shown for ESO Ab+ (n = 8) and ESO Ab− (n = 10) patients with ESO-expressing tumors. Statistical analyses were performed using a two-tailed t-test.

Mentions: The correlation between ESO expression and the ER status found for ESO Ab+ patients prompted us to extend the assessment of ESO expression to a larger group of ER− tumors and a similar group of ER+ tumors from patients in the cohort. Samples were assessed by semi-quantitative PCR and qPCR (Figure 3A and 3B). We found significant ESO expression in 18 (20%) of ER− BC including the 8 patients previously identified through serological analysis and 10 additional patients without detectable ESO Ab. In contrast, we did not find significant levels of ESO expression in the ER+ tumors. The characteristics of ESO Ab− patients with detectable ESO expression and of the corresponding tumors are reported in Table 1 (lower part). Similar to the tumors from ESO Ab+ patients, the majority of the tumors from these patients were high grade and PR−. The large majority was IDC, with 1 diagnosed as MBC and 1 as basal-like cancer (BLC). One of the tumors over-expressed HER2. Three of the patients had a family history of breast cancer, none of them had other tumors and 2 of them had deceased at the time of analysis. Thus, ESO-expressing Ab− patients had characteristics similar to those of the ESO Ab+ group. It is noteworthy that the expression levels of ESO in tumors from ESO Ab+ patients were not significantly different from those found in ESO-expressing tumors from ESO Ab− patients (Figure 3C). We found no significant difference in tumor size between the 2 groups. Interestingly, however, the number of tumor-invaded lymph nodes was, in average, significantly higher in Ab+ patients than in Ab− patients (Figure 3C).


Antibody responses to NY-ESO-1 in primary breast cancer identify a subtype target for immunotherapy.

Hamaï A, Duperrier-Amouriaux K, Pignon P, Raimbaud I, Memeo L, Colarossi C, Canzonieri V, Perin T, Classe JM, Campone M, Jézéquel P, Campion L, Ayyoub M, Valmori D - PLoS ONE (2011)

Assessment of ESO expression in ER− and ER+ BC tumors.A and B. ESO expression in cryopreserved ER− and ER+ BC tumors was assessed by semi-quantitative PCR (A) and qPCR (B). C. The level of ESO expression in the tumor as assessed by qPCR (left panel, mean ± SD), the size of the primary tumor at diagnosis (middle panel, mean ± SD) and the number of tumor-invaded lymph nodes (right panel, mean ± SD) are shown for ESO Ab+ (n = 8) and ESO Ab− (n = 10) patients with ESO-expressing tumors. Statistical analyses were performed using a two-tailed t-test.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3117860&req=5

pone-0021129-g003: Assessment of ESO expression in ER− and ER+ BC tumors.A and B. ESO expression in cryopreserved ER− and ER+ BC tumors was assessed by semi-quantitative PCR (A) and qPCR (B). C. The level of ESO expression in the tumor as assessed by qPCR (left panel, mean ± SD), the size of the primary tumor at diagnosis (middle panel, mean ± SD) and the number of tumor-invaded lymph nodes (right panel, mean ± SD) are shown for ESO Ab+ (n = 8) and ESO Ab− (n = 10) patients with ESO-expressing tumors. Statistical analyses were performed using a two-tailed t-test.
Mentions: The correlation between ESO expression and the ER status found for ESO Ab+ patients prompted us to extend the assessment of ESO expression to a larger group of ER− tumors and a similar group of ER+ tumors from patients in the cohort. Samples were assessed by semi-quantitative PCR and qPCR (Figure 3A and 3B). We found significant ESO expression in 18 (20%) of ER− BC including the 8 patients previously identified through serological analysis and 10 additional patients without detectable ESO Ab. In contrast, we did not find significant levels of ESO expression in the ER+ tumors. The characteristics of ESO Ab− patients with detectable ESO expression and of the corresponding tumors are reported in Table 1 (lower part). Similar to the tumors from ESO Ab+ patients, the majority of the tumors from these patients were high grade and PR−. The large majority was IDC, with 1 diagnosed as MBC and 1 as basal-like cancer (BLC). One of the tumors over-expressed HER2. Three of the patients had a family history of breast cancer, none of them had other tumors and 2 of them had deceased at the time of analysis. Thus, ESO-expressing Ab− patients had characteristics similar to those of the ESO Ab+ group. It is noteworthy that the expression levels of ESO in tumors from ESO Ab+ patients were not significantly different from those found in ESO-expressing tumors from ESO Ab− patients (Figure 3C). We found no significant difference in tumor size between the 2 groups. Interestingly, however, the number of tumor-invaded lymph nodes was, in average, significantly higher in Ab+ patients than in Ab− patients (Figure 3C).

Bottom Line: We found detectable Ab responses to ESO in 1% of the patients.In line with these results, we detected ESO expression in 20% of primary HR⁻ BC, including both ESO Ab⁺ and Ab⁻ patients, but not in HR⁺ BC.Interestingly, whereas expression levels in ESO⁺ BC were not significantly different between ESO Ab⁺ and Ab⁻ patients, the former had, in average, significantly higher numbers of tumor-infiltrated lymph nodes, indicating that lymph node invasion may be required for the development of spontaneous anti-tumor immune responses.

View Article: PubMed Central - PubMed

Affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 892, CLCC René Gauducheau, Saint Herblain, France.

ABSTRACT
The highly immunogenic human tumor antigen NY-ESO-1 (ESO) is a target of choice for anti-cancer immune therapy. In this study, we assessed spontaneous antibody (Ab) responses to ESO in a large cohort of patients with primary breast cancer (BC) and addressed the correlation between the presence of anti-ESO Ab, the expression of ESO in the tumors and their characteristics. We found detectable Ab responses to ESO in 1% of the patients. Tumors from patients with circulating Ab to ESO exhibited common characteristics, being mainly hormone receptor (HR)⁻ invasive ductal carcinomas of high grade, including both HER2⁻ and HER2⁺ tumors. In line with these results, we detected ESO expression in 20% of primary HR⁻ BC, including both ESO Ab⁺ and Ab⁻ patients, but not in HR⁺ BC. Interestingly, whereas expression levels in ESO⁺ BC were not significantly different between ESO Ab⁺ and Ab⁻ patients, the former had, in average, significantly higher numbers of tumor-infiltrated lymph nodes, indicating that lymph node invasion may be required for the development of spontaneous anti-tumor immune responses. Thus, the presence of ESO Ab identifies a tumor subtype of HR⁻ (HER2⁻ or HER2⁺) primary BC with frequent ESO expression and, together with the assessment of antigen expression in the tumor, may be instrumental for the selection of patients for whom ESO-based immunotherapy may complement standard therapy.

Show MeSH
Related in: MedlinePlus