Original Communications| Volume 132, ISSUE 3, P495-501, September 2002

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-γ 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. (Surgery 2002;132:495-501.)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Stein HJ
        • Fink U
        • Siewert JR
        Who benefits from combined modality treatment of esophageal carcinoma?.
        Dis Esoph. 1994; 7: 156-161
        • Stein HJ
        • Sendler A
        • Fink U
        • Siewert JR
        Multidisciplinary approach to esophageal and gastric cancer.
        Surg Clin North Am. 2000; 80: 659-682
        • Nakayama Y
        • Makino S
        • Fukuda Y
        • Min KY
        • Ikemoto T
        • Shimizu A
        • Ohsawa N
        Varied effects of thoracic irradiation on peripheral lymphocyte subsets in lung cancer patients.
        Intern Med. 1995; 34: 959-965
        • Tisch M
        • Heimlich F
        • Daniel V
        • et al.
        Cellular immune defect caused by postsurgical radiation therapy in patients with head and neck cancer.
        Otolaryngol Head Neck Surg. 1998; 119: 412-417
        • Vuckovic-Dekic L
        • Susnjar S
        • Stanojevic-Bakic N
        • Radosavljevic D
        Radio- and chemotherapy variably affect the general immunocompetence of lung cancer patients.
        Panminerva Med. 1999; 41: 129-133
        • Santin AD
        • Hermonat PL
        • Ravaggi A
        • Bellone S
        • Roman J
        • Pecorelli S
        • Cannon M
        • Parham GP
        Effects of concurrent cisplatinum administration during radiotherapy versus radiotherapy alone on the immune function of patients with cancer of the uterine cervix.
        Int J Radiat Oncol Biol Phys. 2000; 48: 997-1006
        • Hensler T
        • Hecker H
        • Heeg K
        • et al.
        Distinct mechanisms of immunosuppression as a consequence of major surgery.
        Infect Immun. 1997; 65: 2283-2291
        • Faist E
        • Schinkel C
        • Zimmer S
        • Kremer JP
        • von Donnersmarck GH
        • Schildberg FW
        Inadequate interleukin-2 synthesis and interleukin-2 messenger expression following thermal and mechanical trauma in humans is caused by defective transmembrane signaling.
        J Trauma. 1993; 34: 846-853
        • Horgan AF
        • Mendez MV
        • O'Riordain DS
        • et al.
        Altered gene transcription after burn injury results in depressed T lymphocyte activation.
        Ann Surg. 1994; 220: 342-351
        • Heidecke CD
        • Hensler T
        • Weighardt H
        • et al.
        Selective defects of T lymphocyte function in patients with lethal intra-abdominal infection.
        Am J Surg. 1999; 178: 288-292
        • Fink U
        • Stein HJ
        • Wilke H
        Multimodal treatment for squamous cell esophageal cancer.
        World J Surg. 1995; 19: 198-204
        • Bosset JF
        • Gignoux M
        • Triboulet JP
        • et al.
        Chemoradiotherapy followed by surgery compared with surgery alone in squamous cell cancer of the esophagus.
        N Engl J Med. 1997; 337: 161-167
        • Cedermark B
        • Johansson H
        • Rutqvist LE
        • Wilking N
        The Stockholm I trial of preoperative short-term radiotherapy in operable rectal carcinoma: a prospective randomized trial.
        Cancer. 1995; 75: 2269-2275
        • Eguchi R
        • Ide H
        • Nakamura T
        • Chu KM
        • Wong J
        Analysis of postoperative complications after esophagectomy for esophageal cancer in patients receiving neoadjuvant therapy.
        Jpn J Thorac Cardiovasc Surg. 1999; 47: 552-558
        • Law S
        • Fok M
        • Chow S
        • Chu KM
        • Wong J
        Preoperative chemotherapy versus surgical therapy alone for squamous cell carcinoma of the esophagus: a prospective randomized trial.
        J Thorac Cardiovasc Surg. 1997; 114: 210-217
        • Kelsen DP
        • Ginsberg R
        • Pajak TF
        • et al.
        Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer.
        N Engl J Med. 1998; 339: 1979-1984
        • Sugimachi K
        • Kitamura M
        • Maekawa S
        • Matsufuji H
        • Kai H
        • Okudarja Y
        Two-stage operation for poor-risk patients with carcinoma of the esophagus.
        J Surg Oncol. 1987; 36: 105-109
        • Saito T
        • Shimoda K
        • Shigemitsu Y
        • Kinoshita T
        • Miyahara M
        • Kobayashi M
        Extensive lymphadenectomy for thoracic esophageal carcinoma: a 2-stage operation for high-risk patients.
        Surg Today. 1994; 24: 610-615
        • DiPierro FV
        • Rice TW
        • DeCamp MM
        • Rybicki LA
        • Blackstone EH
        Esophagectomy and staged reconstruction.
        Eur J Cardiothorac Surg. 2000; 17: 702-709
        • Stein HJ
        • Bartels H
        • Siewert JR
        Esophageal carcinoma: two-stage operation for preventing mediastinitis in high risk patients.
        Chirung. 2001; 72: 831-836