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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 BC tumors from ESO Ab+ patients.ESO expression in cryopreserved BC tumors from ESO Ab+ patients was assessed by semi-quantitative PCR (A) and qPCR (B) using specific primers and ESO+ (SK-MEL-37, Me252) and ESO− (NA8, SK-MEL-23, Me290) tumor cell lines as internal controls.
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pone-0021129-g002: Assessment of ESO expression in BC tumors from ESO Ab+ patients.ESO expression in cryopreserved BC tumors from ESO Ab+ patients was assessed by semi-quantitative PCR (A) and qPCR (B) using specific primers and ESO+ (SK-MEL-37, Me252) and ESO− (NA8, SK-MEL-23, Me290) tumor cell lines as internal controls.

Mentions: The characteristics of the ESO Ab+ patients and of the corresponding tumors are reported in Table 1 (upper part). For 9 of them cryopreserved tumor tissue was available. We assessed ESO expression in these samples by semi-quantitative PCR using previously validated primers (Figure 2A). ESO expression was further confirmed and quantified by qPCR (Figure 2B). Tumor lines and healthy tissues were used as internal controls (Figure 2 and Supporting Figure S1). In support of the results of the serological analysis, we found ESO expression in 8 of the 9 tumors. Tumors from ESO Ab+ patients were mostly invasive ductal carcinomas (IDC), 1 was diagnosed as medullary breast cancer (MBC) and 2 as lymph node metastases with unknown primary. Tumors were of high grade, estrogen receptor (ER)− and progesterone receptor (PR)−. Three of them over-expressed HER2. Five of the patients had a family history of BC, 4 of them had other cancers and 2 of them had deceased at the time of analysis. It is noteworthy that the only patient for whom we could not detect ESO expression in the breast tumor (that at variance with the others was low grade, ER+) was diagnosed with malignant melanoma, that frequently expresses ESO, a few months after the diagnosis of BC.


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 BC tumors from ESO Ab+ patients.ESO expression in cryopreserved BC tumors from ESO Ab+ patients was assessed by semi-quantitative PCR (A) and qPCR (B) using specific primers and ESO+ (SK-MEL-37, Me252) and ESO− (NA8, SK-MEL-23, Me290) tumor cell lines as internal controls.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0021129-g002: Assessment of ESO expression in BC tumors from ESO Ab+ patients.ESO expression in cryopreserved BC tumors from ESO Ab+ patients was assessed by semi-quantitative PCR (A) and qPCR (B) using specific primers and ESO+ (SK-MEL-37, Me252) and ESO− (NA8, SK-MEL-23, Me290) tumor cell lines as internal controls.
Mentions: The characteristics of the ESO Ab+ patients and of the corresponding tumors are reported in Table 1 (upper part). For 9 of them cryopreserved tumor tissue was available. We assessed ESO expression in these samples by semi-quantitative PCR using previously validated primers (Figure 2A). ESO expression was further confirmed and quantified by qPCR (Figure 2B). Tumor lines and healthy tissues were used as internal controls (Figure 2 and Supporting Figure S1). In support of the results of the serological analysis, we found ESO expression in 8 of the 9 tumors. Tumors from ESO Ab+ patients were mostly invasive ductal carcinomas (IDC), 1 was diagnosed as medullary breast cancer (MBC) and 2 as lymph node metastases with unknown primary. Tumors were of high grade, estrogen receptor (ER)− and progesterone receptor (PR)−. Three of them over-expressed HER2. Five of the patients had a family history of BC, 4 of them had other cancers and 2 of them had deceased at the time of analysis. It is noteworthy that the only patient for whom we could not detect ESO expression in the breast tumor (that at variance with the others was low grade, ER+) was diagnosed with malignant melanoma, that frequently expresses ESO, a few months after the diagnosis of BC.

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