Neoadjuvant treatment of esophageal cancer: Immunosuppression following combined radiochemotherapy.
BACKGROUND
The biologic effects of neoadjuvant tumor therapies on the immune system of cancer patients are largely unknown. Immune deviations may be particularly detrimental if they occur in conjunction with postoperative immunosuppression. The effects of combined radiochemotherapy (RCTx) on T cell functions in patients with squamous cell carcinoma of the esophagus were investigated.


METHODS
T cell proliferation was stimulated by incubation of peripheral blood mononuclear cells with bacterial superantigens or by exposure of enriched T cells to superantigens presented by B lymphoma cells. Cytokine production of enriched T cells was induced by cross-linking of CD3 and CD28 and the secretion of interleukin (IL)-2, IL-4, IL-10, and interferon-gamma was measured by enzyme-linked immunosorbent assay. T cell expression of human leukocyte antigen-DR (HLA-DR) molecules was determined by flow cytometry.


RESULTS
T lymphocytes from patients having undergone RCTx exhibited a significantly reduced proliferative response following stimulation with 3 independent superantigens. Cytokine production of T cells and the antigen presenting capacity of patient's peripheral blood mononuclear cells was not diminished following RCTx. T cell expression of HLA-DR was increased following RCTx.


CONCLUSIONS
RCTx of patients with squamous cell carcinoma of the esophagus results in the suppression of T lymphocyte functions. The proliferative defects of T cells after RCTx may be linked to an impaired immune surveillance of cancer and to a higher risk of surgical complications associated with esophagectomy.
D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D016207:Cytokines / Q000096:biosynthesis; D004938:Esophageal Neoplasms / Q000276:immunology / Q000628:therapy*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D000949:Histocompatibility Antigens Class II