Advances in Radiation Therapy. Группа авторов

href="#ulink_37886cbe-01e8-58d9-b7d5-49bb9b86ea21">95]. Preclinical data and available case reports also suggest a superiority of simultaneous regimens or irradiation after the start of immune checkpoint inhibition over a schedule starting with irradiation [63, 69, 96]. The data on the introduction of immunotherapy into normofractionated regimens encompassing adjuvant lymphatic regions applied in neoadjuvant or adjuvant settings and for primary radio(-chemo) therapy is scarce. In addition, the optimal radiation dose, fractionation, and scheduling might differ depending on the immunotherapeutic strategy investigated.

      Conclusion

Immunotherapy is being established as a “fourth pillar” of cancer therapy and is entering the clinic in multiple tumour entities. There is a strong theoretical and preclinical rationale for different immunotherapy strategies stating that the combination of immunotherapy with radiation might be beneficial (Fig. 1). Multiple combination strategies have entered clinical trials (Table 1). However, the details of optimal combination regimens are still under investigation.

      References

1Coley WB: The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin Orthop Relat Res 1991;262:3–11.

2Kienle GS: Fever in cancer treatment: Coley’s therapy and epidemiologic observations. Glob Adv Health Med 2012;1:92–100.

3Wiemann B, Starnes CO: Coley’s toxins, tumor necrosis factor and cancer research: a historical perspective. Pharmacol Ther 1994;64:529–564.

4Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell 2011;144:646–674.

5DeNardo DG, Andreu P, Coussens LM: Interactions between lymphocytes and myeloid cells regulate pro- versus anti-tumor immunity. Cancer Metastasis Rev 2010;29:309–316.

6Grivennikov SI, Greten FR, Karin M: Immunity, inflammation, and cancer. Cell 2010;140:883–899.

7Kim R, Emi M, Tanabe K: Cancer immunoediting from immune surveillance to immune escape. Immunology 2007;121:1–14.

8Teng MW, et al: Immune-mediated dormancy: an equilibrium with cancer. J Leukoc Biol 2008;84:988–993.

9Wolchok JD, et al: Development of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma. Ann NY Acad Sci 2013;1291:1–13.

10Krummel MF, Allison JP: CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 1995;182:459–465.

11Tivol EA, et al: Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 1995;3:541–547.

12Hodi FS, et al: Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010;363:711–723.

13Hodi FS, et al: Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol 2016;17:1558–1568.

14Weber JS, et al: Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2015;16:375–384.

15Singh P, Black P: Emerging role of checkpoint inhibition in localized bladder cancer. Urol Oncol 2016;34:548–555.

      16Longoria TC, Eskander RN: Immune checkpoint inhibition: therapeutic implications in epithelial ovarian cancer. Recent Pat Anticancer Drug Discov 2015;10:133–144.

17Creelan BC: Update on immune checkpoint inhibitors in lung cancer. Cancer Control 2014;21:80–89.

18Rudd CE, Taylor A, Schneider H: CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol Rev 2009;229:12–26.

19Schwartz RH: Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 1992;71:1065–1068.

20Peggs KS, et al: Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr Opin Immunol 2006;18:206–213.

21Quezada SA, et al: CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. J Clin Invest 2006;116:1935–1945.

22D’Incecco A, et al: PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer 2015;112:95–102.

23Velcheti V, et al: Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest 2014;94:107–116.

24Li X, et al: Emerging immune checkpoints for cancer therapy. Acta Oncol 2015;54:1706–1713.

25Finn OJ: Cancer vaccines: between the idea and the reality. Nat Rev Immunol 2003;3:630–641.

26Joura EA, et al: A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med 2015;372:711–723.

27Janakiram NB, et al: Prophylactic vaccine approach for colon and pancreatic cancers: present and future. Curr Med Chem 2012;19:3664–3678.

28Watson CJ, Gusterson BA: A prophylactic vaccine for breast cancer? Breast Cancer Res 2010;12:310.

29Feyerabend