IgG immune response to tumor-associated carbohydrate antigens (TF, Tn, alphaGal) in patients with breast cancer: impact of neoadjuvant chemotherapy and relation to the survival.
OBJECTIVE
To study the humoral immune response to tumor-associated carbohydrate epitopes (TF, Tn and alphaGal) in patients with breast cancer and healthy donors, the putative impact of the chemotherapy and to evaluate if the level of antibody to these epitopes might be beneficial or detrimental for the patients with breast cancer.


METHODS
The humoral immune response to TF, Tn and alphaGal was studied in 133 patients with breast cancer, including the patients at stage II-III (n = 44) before and after neoadjuvant chemotherapy (10 patients received cyclophosphamide/methotrexate/fluorouracyl (CMF) chemotherapy regimens, 34 patients received cyclophosphamide/doxorubicin/fluorouracil (CAF)), and in controls (healthy donors and patients with fibroadenoma). Fully synthetic carbohydrate hapten-polyacrylamide conjugates were used as antigens in ELISA for anti-carbohydrate antibody determination. The correlation analysis between the level of anti-carbohydrate antibodies and the stage of cancer, histological grade, expression of TF and alphaGal epitopes in tumor tissue, patient's survival was performed.


RESULTS
The level of anti-carbohydrate antibodies varied between individuals with no significant correlation between IgG immune response to the three epitopes. Lower levels of antibodies were observed at advanced stages of cancer. Neoadjuvant chemotherapy stimulated antibody production to Tn and alphaGal epitopes (increase > 50%) in about one third of patients. Immunosuppression, decrease in antibody levels, was observed only in 4.5-13.6% of cases. High levels of TF-antigen specific IgG antibody before surgery were associated with a better survival time of stage II breast cancer patients.


CONCLUSIONS
The widely used regimens of neoadjuvant chemotherapy (such as CMF, CAF) can stimulate the immune response to tumor-associated carbohydrate epitopes in some patients. The high levels of anti-TF antibody before surgery are associated with a better survival of stage II breast cancer patients. This may indicate that the selection of immunopotentiating regimens of neoadjuvant chemotherapy might be beneficial for the host.
Kurtenkov
O
O
National Institute for Health Development, Tallinn 11619, Estonia. oleg.kurtenkov@tai.ee
Klaamas
K
K
Rittenhouse-Olson
K
K
Vahter
L
L
Sergejev
B
B
Miljukhina
L
L
Shljapnikova
L
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000032:analysis*; D000917:Antibody Formation; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D000939:Epitopes; D005260:Female; D018226:Fibroadenoma / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D005472:Fluorouracil / Q000008:administration & dosage; D006241:Haptens; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D015996:Survival Rate; D013925:Thromboplastin / Q000276:immunology; D000519:alpha-Galactosidase / Q000276:immunology
D000912:Antibodies, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D000939:Epitopes; D006241:Haptens; C040286:Tn antigen; C016467:Thomsen-Friedenreich antigen; D004317:Doxorubicin; D003520:Cyclophosphamide; D013925:Thromboplastin; D000519:alpha-Galactosidase; D005472:Fluorouracil; D008727:Methotrexate