OJAnes  Vol.3 No.3 , May 2013
Perioperative Clinical Interventions That Modify the Immune Response in Cancer Patients
Abstract: The immune system plays a pivotal role against cancer. The development of a successful immune response involves the balance between the Th1 (antitumor) and Th2 (protumor) responses. Once this balance is lost, diseases such as cancer may become apparent. Surgical stress, volatile anaesthetics, opioids and blood transfusions are known to favour a Th2 response that manifests as immune suppression. During surgery the load of circulating malignant cancer cells is increased by tumour manipulation. These cancer cells can migrate and seed in distant tissues and form metastasis. Also, some cancer patients may present with micrometastasis that may become invasive if left untreated. Therefore, the perioperative period is a moment of immunological vulnerability in cancer patients. A better understanding of the factors that affect the Th1/Th2 balance may allow anaesthesiologists to identify patients at high risk for cancer recurrence. This review describes the perioperative interventions that can alter the Th1/Th2 balance, during the perioperative period of oncological surgery.
Cite this paper: M. Ramírez, J. Huitink and J. Cata, "Perioperative Clinical Interventions That Modify the Immune Response in Cancer Patients," Open Journal of Anesthesiology, Vol. 3 No. 3, 2013, pp. 133-139. doi: 10.4236/ojanes.2013.33031.

[1]   J. E. Talmadge, K. M. Meyers, D. J. Prieur and J. R. Starkey, “Role of NK Cells in Tumour Growth and Metastasis in Beige Mice,” Nature, Vol. 284, No. 5757, 1980, pp. 622-624.

[2]   S. Goto, M. Sato, R. Kaneko, M. Itoh, S. Sato and S. Takeuchi, “Analysis of Th1 and Th2 Cytokine Production by Peripheral Blood Mononuclear Cells as a Parameter of Immunological Dysfunction in Advanced Cancer Patients,” Cancer Immunology, Immunotherapy, Vol. 48, No. 8, 1999, pp. 435-442.

[3]   T. R. Mosmann and R. L. Coffman, “TH1 and TH2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional Properties,” Annual Review of Immunology, Vol. 7, No. 1, 1989, pp. 145-173. doi:10.1146/annurev.iy.07.040189.001045

[4]   T. R. Malek and A. L. Bayer, “Tolerance, Not Immunity, Crucially Depends on IL-2,” Natural Review of Immunology, Vol. 4, No. 9, 2004, pp. 665-674.

[5]   B. H. Li, S. B. Xu, F. Li, X. G. Zou, A. Saimaiti, D. Simayi, et al., “Stat6 Activity-Related Th2 Cytokine Profile and Tumor Growth Advantage of Human Colorectal Cancer Cells in Vitro and in Vivo,” Cell Signal, Vol. 24, No. 3, 2012, pp. 718-725.

[6]   R. Kim, M. Emi and K. Tanabe, “Cancer Immunosuppression and Autoimmune Disease: Beyond Immunosuppressive Networks for Tumour Immunity,” Immunology, Vol. 119, No. 2, 2006, pp. 254-264.

[7]   R. Vallejo, E. D. Hord, S. A. Barna, J. Santiago-Palma and S. Ahmed, “Perioperative Immunosuppression in Cancer Patients,” Journal of Environmental Pathology, Toxicology and Oncology: Official Organ of the International Society for Environmental Toxicology and Cancer, Vol. 22, No. 2, 2003, pp. 139-146.

[8]   T. Udagawa, “Tumor Dormancy of Primary and Secondary Cancers,” Apmis, Vol. 116, No. 7-8, 2008, pp. 615-628.

[9]   V. W. Rusch, D. Hawes, P. A. Decker, S. E. Martin, A. Abati, R. J. Landreneau, et al., “Occult Metastases in Lymph Nodes Predict Survival in Resectable Non-Small-Cell Lung Cancer: Report of the ACOSOG Z0040 Trial,” Journal of Clinical Oncology, Vol. 29, No. 32, 2011, pp. 4313-4319.

[10]   C. Y. Lu, Y. H. Uen, H. L. Tsai, S. C. Chuang, M. F. Hou, D. C. Wu, et al., “Molecular Detection of Persistent Postoperative Circulating Tumour Cells in Stages II and III Colon Cancer Patients via Multiple Blood Sampling: Prognostic Significance of Detection for Early Relapse,” British Journal of Cancer, Vol. 104, No. 7, 2011, pp. 1178-1184.

[11]   C. M. Koebel, W. Vermi, J. B. Swann, N. Zerafa, S. J. Rodig, L. J. Old, et al., “Adaptive Immunity Maintains Occult Cancer in an Equilibrium State,” Nature, Vol. 450, No. 7171, 2007, pp. 903-907.

[12]   J. P. Cata, V. Gottumukkala and D. I. Sessler, “How Regional Anesthesia Might Reduce Postoperative Cancer Recurrence,” European Journal of Pain Supplement, Vol. 5, No. S2, 2012, pp. 345-355.

[13]   H. Tatsumi, H. Ura, S. Ikeda, K. Yamaguchi, T. Katsuramaki, Y. Asai, et al., “Surgical Influence on TH1/TH2 Balance and Monocyte Surface Antigen Expression and Its Relation to Infectious Complications,” World Journal of Surgery, Vol. 27, No. 5, 2003, pp. 522-528.

[14]   D. Decker, M. Schondorf, F. Bidlingmaier, A. Hirner and A. A. von Ruecker, “Surgical Stress Induces a Shift in the Type-1/Type-2 T-Helper Cell Balance, Suggesting Down-Regulation of Cell-Mediated and Up-Regulation of Antibody-Mediated Immunity Commensurate to the Trauma,” Surgery, Vol. 119, No. 3, 1996, pp. 316-325.

[15]   M. Ishikawa, M. Nishioka, N. Hanaki, T. Miyauchi, Y. Kashiwagi, H. Ioki, et al., “Perioperative Immune Responses in Cancer Patients Undergoing Digestive Surgeries,” World Journal of Surgical Oncology, Vol. 7, No. 7, 2009, p. 7. doi:10.1186/1477-7819-7-7

[16]   N. Sato, K. Koeda, Y. Kimura, K. Ikeda, M. Ogawa and K. Saito, et al., “Cytokine Profile of Serum and Bronchoalveolar Lavage Fluids Following Thoracic Esophageal Cancer Surgery,” European Surgical Research, Vol. 33, No. 4, 2001, pp. 279-284.

[17]   C. W. Strey, R. M. Marquez-Pinilla, M. M. Markiewski, B. Siegmund, E. Oppermann, J. D. Lambris, et al., “Early Post-Operative Measurement of Cytokine Plasma Levels Combined with Pre-Operative Bilirubin Levels Identify High-Risk Patients after Liver Resection,” International Journal of Molecular Medicine, Vol. 27, No. 3, 2011, pp. 447-454.

[18]   M. Zelic, D. Stimac, D. Mendrila, V. S. Tokmadzic, E. Fisic, M. Uravic, et al., “Influence of Preoperative Oral Feeding on Stress Response after Resection for Colon Cancer,” Hepato-Gastroenterology, Vol. 59, No. 117, 2012, pp. 1385-1389.

[19]   R. Berguer, N. Bravo, M. Bowyer, C. Egan, T. Knolmaye and D. Ferrick, “Major Surgery Suppresses Maximal Production of Helper T-Cell Type 1 Cytokines without Potentiating the Release of Helper T-Cell Type 2 Cytokines,” Archives of Surgery, Vol. 134, No. 5, 1999, pp. 540-544.

[20]   H. W. Huang, J. L. Tang, X. H. Han, Y. P. Peng and Y. H. Qiu, “Lymphocyte-Derived Catecholamines Induce a Shift of Th1/Th2 Balance toward Th2 Polarization,” Neuroimmunomodulation, Vol. 20, No. 1, 2012, pp. 1-8.

[21]   F. Greco, M. R. Hoda, N. Mohammed, C. Springer, K. Fischer and P. Fornara, “Laparoendoscopic Single-Site and Conventional Laparoscopic Radical Nephrectomy Result in Equivalent Surgical Trauma: Preliminary Results of a Single-Centre Retrospective Controlled Study,” European Urology, Vol. 61, No. 5, 2012, pp. 1048-1053.

[22]   K. Galaal, A. Bryant, A. D. Fisher, M. Al-Khaduri, F. Kew and A. D. Lopes AD, “Laparoscopy versus Laparotomy for the Management of Early Stage Endometrial Cancer,” Cochrane Database Systematic Review, Vol. 9, 2012, Article ID: CD006655.

[23]   A. C. Gordon, K. Kojima, M. Inokuchi, K. Kato and K. Sugihara, “Long-Term Comparison of Laparoscopy-Assisted Distal Gastrectomy and Open Distal Gastrectomy in Advanced Gastric Cancer,” 2012.

[24]   G. Di Vita, C. Sciume, S. Milano, R. Patti, G. L. Lauria, G. Di Bella, et al., “Th1-Like and Th2-Like Cytokines in Patients Undergoing Open versus Laparascopic Cholecystectomy,” Annali Italiani di Chirurgia, Vol. 72, No. 4, 2001, pp. 485-491.

[25]   J. P. Desborough, “The Stress Response to Trauma and Surgery,” British Journal of Anaesthetic, Vol. 85, No. 1, 2000, pp. 109-117.

[26]   D. Tsamis, G. Theodoropoulos, P. Stamopoulos, S. Siakavellas, T. Delistathi, N. V. Michalopoulos, et al., “Systemic Inflammatory Response after Laparoscopic and Conventional Colectomy for Cancer: A Matched Case-Control Study,” Surgical Endoscopy, Vol. 26, No. 5, 2012, pp. 1436-1443.

[27]   H. Tsujimoto, R. Takahata, S. Nomura, Y. Yaguchi, I. Kumano, Y. Matsumoto, et al., “Video-Assisted Thoracoscopic Surgery for Esophageal Cancer Attenuates Postoperative Systemic Responses and Pulmonary Complications,” Surgery, Vol. 151, No. 5, 2012, pp. 667-673.

[28]   Z. Li, H. Liu and L. Li, “Video-Assisted Thoracoscopic Surgery versus Open Lobectomy for Stage I Lung Cancer: A Meta-Analysis of Long-Term Outcomes,” Experimental Therapeutic Medicine, Vol. 3, No. 5, 2012, pp. 886-892.

[29]   B. L. Green, H. C. Marshall, F. Collinson, P. Quirke, P. Guillou, D. G. Jayne, et al., “Long-Term Follow-Up of the Medical Research Council CLASICC Trial of Conventional versus Laparoscopically Assisted Resection in Colorectal Cancer,” British Journal of Surgery, Vol. 100, No. 1, 2013, pp. 75-82.

[30]   H. Ichikawa, G. Miyata, S. Miyazaki, K. Onodera, T. Kamei, T. Hoshida, et al., “Esophagectomy Using a Thoracoscopic Approach with an Open Laparotomic or Hand-Assisted Laparoscopic Abdominal Stage for Esophageal Cancer: Analysis of Survival and Prognostic Factors in 315 Patients,” 2012.

[31]   V. Weisbach, C. Wanke, J. Zingsem, R. Zimmermann and R. Eckstein, “Cytokine Generation in Whole Blood, Leukocyte-Depleted and Temporarily Warmed Red Blood Cell Concentrates,” Vox Sanguinis, Vol. 76, No. 2, 1999, pp. 100-106.

[32]   G. Stack, L. Baril, P. Napychank and E. L. Snyder, “Cytokine Generation in Stored, White Cell-Reduced, and Bacterially Contaminated Units of Red Cells,” Transfusion, Vol. 35, No. 3, 1995, pp. 199-203.

[33]   A. Shanwell, M. Kristiansson, M. Remberger and O. Ringden, “Generation of Cytokines in Red Cell Concentrates during Storage Is Prevented by Prestorage White Cell Reduction,” Transfusion, Vol. 37, No. 7, 1997, pp. 678-684.

[34]   O. Karam, M. Tucci, B. J. Toledano, N. Robitaille, J. Cousineau, L. Thibault, et al., “Length of Storage and in Vitro Immunomodulation Induced by Prestorage Leukoreduced Red Blood Cells,” Transfusion, Vol. 49, No. 11, 2009, pp. 2326-2334.

[35]   M. B. Patel, K. G. Proctor and M. Majetschak, “Extracellular Ubiquitin Increases in Packed Red Blood Cell Units during Storage,” The Journal of Surgical Research, Vol. 135, No. 2, 2006, pp. 226-232.

[36]   J. M. Baumgartner, C. C. Silliman, E. E. Moore, A. Banerjee and M. D. McCarter, “Stored Red Blood Cell Transfusion Induces Regulatory T Cells,” Journal of the American College of Surgeons, Vol. 208, No. 1, 2009, pp. 110-119.

[37]   A. E. Biedler, S. O. Schneider, U. Seyfert, H. Rensing, S. Grenner, M. Girndt, et al., “Impact of Alloantigens and Storage-Associated Factors on Stimulated Cytokine Response in An in Vitro Model of Blood Transfusion,” Anesthesiology, Vol. 97, No. 5, 2002, pp. 1102-1109.

[38]   T. S. Creasy, P. S. Veitch and P. R. Bell, “A Relationship Between Perioperative Blood Transfusion and Recurrence of Carcinoma of the Sigmoid Colon Following Potentially Curative Surgery,” Annals of the Royal College of Surgeons of England, Vol. 69, No. 3, 1987, pp. 100-103.

[39]   D. W. Moores, S. Piantadosi and M. F. McKneally, “Effect of Perioperative Blood Transfusion on Outcome in Patients with Surgically Resected Lung Cancer,” The Annals of Thoracic Surgery, Vol. 47, No. 3, 1989, pp. 346-351.

[40]   R. Chesi, A. Cazzola, G. Bacci, B. Borghi, A. Balladelli and G. Urso, “Effect of Perioperative Transfusions on Survival in Osteosarcoma Treated by Multimodal Therapy,” Cancer, Vol. 64, No. 8, 1989, pp. 1727-1737.

[41]   A. Amato and M. Pescatori, “Perioperative Blood Transfusions for the Recurrence of Colorectal Cancer,” Cochrane Database of Systematic Reviews, Vol. 1, 2006, Article ID: CD005033.

[42]   K. M. Greeneltch, A. E. Kelly-Welch, Y. Shi and A. D. Keegan, “Chronic Morphine Treatment Promotes Specific Th2 Cytokine Production by Murine T Cells in Vitro via A Fas/Fas Ligand-Dependent Mechanism,” The Journal of Immunology, Vol. 175, No. 8, 2005, pp. 4999-5005.

[43]   S. Roy, S. Balasubramanian, S. Sumandeep, R. Charboneau, J. Wang, D. Melnyk, et al., “Morphine Directs T Cells toward T(H2) Differentiation,” Surgery, Vol. 130, No. 2, 2001, pp. 304-309.

[44]   C. Borner, B. Warnick, M. Smida, R. Hartig, J. A. Lindquist, B. Schraven, et al., “Mechanisms of Opioid-Mediated Inhibition of Human T Cell Receptor Signaling,” The Journal of Immunology, Vol. 183, No. 2, 2009, pp. 882-889.

[45]   Q. Y. Zhang, M. Zhang and Y. Cao, “Exposure to Morphine Affects the Expression of Endocannabinoid Receptors and Immune Functions,” Journal of Neuroimmunology, Vol. 247, No. 1-2, 2012, pp. 52-58.

[46]   J. Kraus, L. Lehmann, C. Borner and V. Hollt, “Epigenetic Mechanisms Involved in the Induction of the Mu Opioid Receptor Gene in Jurkat T Cells in Response to Interleukin-4,” Molecular Immunology, Vol. 48, No. 1-3, 2010, pp. 257-263.

[47]   I. Z. Yardeni, B. Beilin, E. Mayburd, Y. Alcalay and H. Bessler, “Relationship between Fentanyl Dosage and Immune Function in the Postoperative Period,” Journal of Opioid Management, Vol. 4, No. 1, 2008, pp. 7-33.

[48]   R. Pacifici, S. di Carlo, A. Bacosi, S. Pichini and P. Zuccaro, “Pharmacokinetics and Cytokine Production in Heroin and Morphine-Treated Mice,” International Journal of Immunopharmacology, Vol. 22, No. 8, 2000, pp. 603-614.

[49]   M. H. Kim and T. S. Hahm, “Plasma Levels of Interleukin-6 and Interleukin-10 Are Affected by Ketorolac as an Adjunct to Patient-Controlled Morphine after Abdominal Hysterectomy,” The Clinical Journal of Pain, Vol. 17, No. 1, 2001, pp. 72-77.

[50]   C. A. Deegan, D. Murray, P. Doran, D. C. Moriarty, D. I. Sessler, E. Mascha, et al., “Anesthetic Technique and the Cytokine and Matrix Metalloproteinase Response to Primary Breast Cancer Surgery,” Regional Anesthesia and Pain Medicine, Vol. 35, No. 6, 2010, pp. 490-495. doi:10.1097/AAP.0b013e3181ef4d05

[51]   C. E. Schneemilch, T. Hachenberg, S. Ansorge, A. Ittenson and U. Bank, “Effects of Different Anaesthetic Agents on Immune Cell Function in Vitro,” European Journal of Anaesthesiology, Vol. 22, No. 8, 2005, pp. 616-623.

[52]   J. M. Brand, C. Frohn, J. Luhm, H. Kirchner and P. Schmucker, “Early Alterations in the Number of Circulating Lymphocyte Subpopulations and Enhanced Proinflammatory Immune Response during Opioid-Based General Anesthesia,” Shock, Vol. 20, No. 3, 2003, pp. 213-217.

[53]   J. M. Brand, H. Kirchner, C. Poppe and P. Schmucker, “The Effects of General Anesthesia on Human Peripheral Immune Cell Distribution and Cytokine Production,” Clinical Immunology and Immunopathology, Vol. 83, No. 2, 1997, pp. 190-194.

[54]   M. Salo, C. O. Pirttikangas and K. Pulkki, “Effects of Propofol Emulsion and Thiopentone on T Helper Cell Type-1/Type-2 Balance in Vitro,” Anaesthesia, Vol. 52, No. 4, 1997, pp. 341-344.

[55]   X. F. Ren, W. Z. Li, F. Y. Meng and C. F. Lin, “Differential Effects of Propofol and Isoflurane on the Activation of T-Helper Cells in Lung Cancer Patients,” Anaesthesia, Vol. 65, No. 5, 2010, pp. 478-482.

[56]   N. Ohta, Y. Ohashi and Y. Fujino, “Ketamine Inhibits Maturation of Bone Marrow-Derived Dendritic Cells and Priming of the Th1-Type Immune Response,” Anesthesia & Analgesia, Vol. 109, No. 3, 2009, pp. 793-800.

[57]   C. E. Schneemilch, A. Ittenson, S. Ansorge, T. Hachenberg and U. Bank, “Effect of 2 Anesthetic Techniques on the Postoperative Proinflammatory and Anti-Inflammatory Cytokine Response and Cellular Immune Function to Minor Surgery,” Journal of Clinical Anesthesia, Vol. 17, No. 7, 2005, pp. 517-527.

[58]   G. Delogu, A. Antonucci, M. Signore, M. Marandola, G. Tellan and F. Ippoliti, “Plasma Levels of Il-10 and Nitric Oxide under Two Different Anaesthesia Regimens,” European Journal of Anaesthesiology, Vol. 22, No. 6, 2005, pp. 462-466.

[59]   S. Bar-Yosef, R. Melamed, G. G. Page, G. Shakhar, K. Shakhar and S. Ben-Eliyahu, “Attenuation of the Tumor-Promoting Effect of Surgery by Spinal Blockade in Rats,” Anesthesiology, Vol. 94, No. 6, 2001, pp. 1066-1073.

[60]   H. Wada, S. Seki, T. Takahashi, N. Kawarabayashi, H. Higuchi, Y. Habu, et al., “Combined Spinal and General Anesthesia Attenuates Liver Metastasis by Preserving Th1/Th2 Cytokine Balance,” Anesthesiology, Vol. 106, No. 3, 2007, pp. 499-506.

[61]   M. Zura, A. Kozmar, K. Sakic, B. Malenica and Z. Hrgovic, “Effect of Spinal and General Anesthesia on Serum Concentration of Pro-Inflammatory and Anti-Inflammatory Cytokines,” 2011.

[62]   A. E. Le Cras, H. F. Galley and N. R. Webster, “Spinal but Not General Anesthesia Increases the Ratio of T Helper 1 to T Helper 2 Cell Subsets in Patients Undergoing Transurethral Resection of the Prostate,” Anesthesia and Analgesia, Vol. 87, No. 6, 1998, pp. 1421-1425.

[63]   O. Ahlers, I. Nachtigall, J. Lenze, A. Goldmann, E. Schulte, C. Hohne, et al., “Intraoperative Thoracic Epidural Anaesthesia Attenuates Stress-Induced Immunosuppression in Patients Undergoing Major Abdominal Surgery,” British Journal of Anaesthesia, Vol. 101, No. 6, 2008, pp. 781-787.

[64]   E. Viviano, M. Renius, J. C. Ruckert, A. Bloch, C. Meisel, A. Harbeck-Seu, et al., “Selective Neurogenic Blockade and Perioperative Immune Reactivity in Patients Undergoing Lung Resection,” Journal of International Medical Research, Vol. 40, No. 1, 2012, pp. 141-156.

[65]   J. P. Cata, V. Gottumukkala and D. I. Sessler, “How Regional Analgesia Might Reduce Postoperative Cancer Recurrence,” European Journal of Pain Supplements, Vol. 5, No. 2, 2011, pp. 345-355.

[66]   D. I. Sessler, “Does Regional Analgesia Reduce the Risk of Cancer Recurrence? A Hypothesis,” European Journal of Cancer Prevention, Vol. 17, No. 3, 2008, pp. 269-272.