Effects of Thermotherapy on Th1/Th2 Cells in Esophageal Cancer Patients Treated with Radiotherapy

  • Hong, Mei (Department of Radiotherapy, Nanjing Thoracic Hospital) ;
  • Jiang, Zao (Department of Oncology, Zhongda Hospital Affiliated to Southeast University) ;
  • Zhou, Ying-Feng (Department of Radiotherapy, Nanjing Jiangbei People's Hospital)
  • Published : 2014.03.01


Background: To investigate the effects of double radiofrequency hyperthermia on Th1/Th2 cells in esophageal cancer patients treated with radiotherapy. Materials and Methods: 22 patients with esophageal cancer were divided into a radiotherapy group (10 cases) and a combined group (double radiofrequency hyperthermia combined with radiotherapy group, 12 cases). Both groups received conventional radiotherapy using a cobalt-60 therapy apparatus (TD60-66Gy/30-33F). Patients in the combined group also underwent double radiofrequency hyperthermia (2F/W, 8-10F). Before and after treatment, Th1, Th2, Tc1 and Tc2 cells in peripheral blood were determined with flow cytometry. Results: In the radiotherapy group, Th1 cell contents before and after radiotherapy were $17.5{\pm}5.26%$ and $9.69{\pm}4.86%$, respectively, with a significant difference (p<0.01). The Th1/Th2 ratio was significantly decreased from $28.2{\pm}14.3$ to $16.5{\pm}10.4 $(p<0.01). In the combined group, Th1 cell content before radiotherapy was $15.9{\pm}8.18%$, and it increased to $18.6{\pm}8.84$ after radiotherapy (p>0.05), the Th1/Th2 ratio decreasing from $38.4{\pm}36.3$ to $28.1{\pm}24.0$ (p>0.05). Changes in Th2, Tc1 and Tc2 cell levels were not significant in the two groups before and after therapy (p>0.05). Conclusions: Double radiofrequency hyperthermia can promote the conversion from Th2 to Th1 cells, and regulate the balance of Th1/Th2 cells.


  1. Abbas AK, Murphy KM, Sher A (1996). Function diversity of helper T lymphocytes. Nature, 383, 787-93.
  2. Ahlers O, Hilderbrant B, Dieing A (2005). Stress induced changes in lymphocyte subpopulations and associated cytokines during whole body hyperthermia of 41.8-42.2 degree C. Eur J Appl Physiol, 95, 298-306.
  3. Almhanna K, Shridhar R, Meredith KL (2013). Neoadjuvant or adjuvant therapy for resectable esophageal cancer: is there a standard of care. Cancer Control, 20, 89-96.
  4. Bottaro DP, Liotta LA (2003). Cancer: Out of air is not out of action. Nature, 423, 593-5.
  5. Braumuller H, Wieder T, Brenner E, et al (2013). T-helper-1-cell cytokines drive cancer into senescence. Nature, 494, 361-5.
  6. Dings RP, Loren ML, Zhang Y, et al (2011). Tumour thermotolerance, a physiological phenomenon involving vessel normalisation. Int J Hyperthermia, 27, 42-52.
  7. Griffin RJ, Dings RP, Jamshidi-Parsian A, et al (2010). Mild temperature hyperthermia and radiation therapy: Role of tumour vascular thermotolerance and relevant physiological factors. Int J Hyperthermia, 26, 256-63.
  8. Kobayashi M, Kubo T, Komatsu K, et al (2013). Changes in peripheral blood immune cells: their prognostic significance in metastatic renal cell carcinomapatients treated with molecular targeted therapy. Med Oncol, 30, 556.
  9. Magdalena C, Anna D, Krystyna S, et al (2004). Sera of lung cancer patients affect the release of Th1, Th2 and monocytederived cytokines, and the expression of TL-$2R\alpha$ by normal, stimulated mononuclear cells. Mol Cell Biol Lett, 9, 69-81.
  10. Morita M, Kuwano H, Araki K, et al (2001). Prognostic significance of lymphocyte infiltration following properative chemoradiotherapy and hyperthermia for esoph-ageal cancer. Int J Radiat Oncol Biol Phys, 49, 1259-66.
  11. Mosmann TR, Cherwinski H, Bond MW, et al (1986). Two types of murme helper Tcell clone I. Defintion according to profiles of lymphokine activities and secreted proteins. J Immunol, 136, 2348-57.
  12. Rotstein S, Blomgren H, Petrini B, et al (1985). Long term effects on the immune system following local radiation therapy for breast cancer. I. Cellular composition of the peripheral blood lymphocyte population. Int J Radiat Oncol Biol Phys, 11, 921-5.
  13. Cui YH, Liang HJ, Zhang QQ, et al (2012). Radiosensitivity enhancement by arsenic trioxide in conjunction with hyperthermia in the EC-1 esophageal carcinoma cell line. Asian Pac J Cancer Prev, 13, 1693-7.
  14. Wang DC, Zhang Y, Chen HY, et al (2012). Hyperthermia promotes apoptosis and suppresses invasion in C6 rat glioma cells. Asian Pac J Cancer Prev. 13, 3239-45.
  15. Zhou HM, Feng B, Zhao HC, et al (2012). Antitumor effects of hyperthermic CO2 pneumoperitoneum on human gastric cancer cells. Asian Pac J Cancer Prev, 13, 117-22.
  16. Saga T, Sakahara H, Nakamoto Y, et al (2002). Enhancement of the therapeutic outcome of radio-immunotherapy by combination with wholebody mild hyperthermia. Eur J Cancer, 86, 1579-603.
  17. Song PI, Liang H, Fan JH, et al (2011). Long-term survival after esophagectomy for early esophageal squamous cell carcinoma in Linxian, China. J Surg Oncol, 104, 176-80.
  18. Tsukui T, Hildesheim A, Schiffman MH, et al (1996). Interleukin-2 production in vitro by perrpheral lymphocytes in response to human papillomavirus-derived peptides: correlation with cervical pathology. Cancer Res, 56, 3967-74.
  19. Wang Q, Chen DY (2009). Effect of Aidi injection on peripheral blood expression of Th1/Th2 transcription factors and cytokines in patients with esophageal squamous cell carcinoma during radiotherapy. Chinese J Integ Tradition West Med, 29, 394-7.
  20. Wang XY, Kazim L, Repasky EA, et al (2001). Characterization of heat shock protein 110 and glucose-related protein 170 as cancer vaccines and the effect of fever range hyperthermia on accine activity. J Immunol, 166, 490-7.
  21. Westerterp M, Boermeester MA, Omloo JM, et al (2008). Differential responses of cellular immunity in patients undergoing neoadjuvant therapy followed by surgery forcarcinoma of the oesophagus. Cancer Immunol Immunother, 57, 1837-47.
  22. Yuguchi T, Saito M, Yokoyama Y, et al (2002). Combined use of hyperthermia and irradiation cause antiproliferative activity and cell death to human esophageal cell carcinoma cells-mainly cell cycle examination. Hum Cell, 15, 33-42.
  23. Zhao JX, Li XF, Wang XX (2007). Effects of body-resistance strengthening and tumor-suppressing granules on immune adhesion function of red blood cells and expression of metastasis protein CD44 in tumor cells of patients with esophageal carcinoma. World J Gastroenterol, 13, 4360-4.
  24. Zolzer F, Streffer C (2001). G2-Phase delays after irradiation and/or heat treatment as assessed by two-parameter flow cytometry. Radiat Res, 155, 50-6.[0050:GPDAIA]2.0.CO;2

Cited by

  1. Induction of Indoleamine 2,3-dioxygenase (IDO) Enzymatic Activity Contributes to Interferon-Gamma Induced Apoptosis and Death Receptor 5 Expression in Human Non-small Cell Lung Cancer Cells vol.15, pp.18, 2014,
  2. Interferon gamma-induced apoptosis of head and neck squamous cell carcinoma is connected to indoleamine-2,3-dioxygenase via mitochondrial and ER stress-associated pathways vol.11, pp.1, 2016,
  3. Impairment of the Intrinsic Capability of Th1 Polarization in Irradiated Mice: A Close Look at the Imbalanced Th1/Th2 Response after Irradiation vol.186, pp.6, 2016,