Der Pathologe

, Volume 39, Issue 6, pp 492–497 | Cite as

Immunologische Grundlagen moderner (Tumor‑)Immuntherapie

  • T. Bopp
  • H. SchildEmail author
Schwerpunkt: Immunpathologie


Die Voraussetzung für die Entwicklung zielgerichteter Strategien zur Beeinflussung des Immunsystems bei der Bekämpfung von Krebserkrankungen sowie zur Förderung und Konzeption neuer Therapieansätze ist, grundlegende Prinzipien hinter der Entstehung, Aktivierung, Regulierung und dem Absterben von Immunzellen sowie die molekularen Mechanismen hinter der Diversifikation und Plastizität des Immunsystems zu verstehen. Die Translation dieser grundlegenden Prinzipien hat in den letzten Jahren zur Entwicklung bahnbrechender Therapieansätze in der Behandlung von Tumorerkrankungen geführt.


Aktive Immuntherapie Immunevasion Immunologische Checkpoint Inhibitoren Tumoren Tumorescape 

Immunological foundations of modern (tumor) immunotherapy


Understanding the fundamental principles underlying the development, activation, regulation, plasticity, diversification, and even death of immune cells is a prerequisite for the development of targeted strategies to modulate the immune system in the fight against cancer. As our understanding of these processes evolves, their translation has led to the development of pioneering therapeutic approaches in the treatment of malignant diseases.


Active immunotherapy Immune evasion Immune checkpoint inhibitors Neoplasms Tumor escape 


Einhaltung ethischer Richtlinien


T. Bopp und H. Schild geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.


  1. 1.
    Anderson AC, Joller N, Kuchroo VK (2016) Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity 44:989–1004. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Barber DL, Wherry EJ, Masopust D et al (2006) Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439:682–687. CrossRefPubMedGoogle Scholar
  3. 3.
    Blank C, Mackensen A (2007) Contribution of the PD-L1/PD-1 pathway to T‑cell exhaustion: an update on implications for chronic infections and tumor evasion. Cancer Immunol Immunother 56:739–745. CrossRefGoogle Scholar
  4. 4.
    Brahmer JR, Tykodi SS, Chow LQM et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Chen DS, Mellman I (2013) Oncology meets immunology: the cancer-immunity cycle. Immunity 39:1–10. CrossRefGoogle Scholar
  6. 6.
    Diem S, Kasenda B, Spain L et al (2016) Serum lactate dehydrogenase as an early marker for outcome in patients treated with anti-PD-1 therapy in metastatic melanoma. Br J Cancer 114:256–261. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Dunn GP, Bruce AT, Ikeda H et al (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3:991–998. CrossRefGoogle Scholar
  8. 8.
    Dvorak HF, Dvorak HF (2015) Tumors: wounds that do not heal-redux. Cancer Immunol Res 3:1–11. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Evans R, Alexander P (1970) Cooperation of immune lymphoid cells with macrophages in tumour immunity. Nature 228:620–622CrossRefGoogle Scholar
  10. 10.
    Gabrilovich DI, Ostrand-Rosenberg S, Bronte V (2012) Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 12:253–268. CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Gerlinger M, Rowan AJ, Horswell S et al (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366:883–892. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Grupp SA, Kalos M, Barrett D et al (2013) Chimeric antigen receptor–modified T cells for acute lymphoid leukemia. N Engl J Med 368:1509–1518. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Hammers HJ, Plimack ER, Infante JR et al (2017) Safety and efficacy of nivolumab in combination with Ipilimumab in metastatic renal cell carcinoma: the checkmate 016 study. J Clin Oncol 72(2016):198–113. CrossRefGoogle Scholar
  14. 14.
    Hodi FS, O’Day SJ, McDermott DF et al (2010) Improved survival with Ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Johnson LA, Morgan RA, Dudley ME et al (2009) Gene therapy with human and mouse T‑cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 114:535–546. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Kalos M, June CH (2013) Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology. Immunity 39:49–60. CrossRefPubMedGoogle Scholar
  17. 17.
    Kenter GG, Welters MJP, Valentijn ARPM et al (2009) Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia. N Engl J Med 361:1838–1847. CrossRefPubMedGoogle Scholar
  18. 18.
    Kim JM, Chen DS (2016) Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure). Ann Oncol 27:1492–1504. CrossRefPubMedGoogle Scholar
  19. 19.
    Kochenderfer JN, Rosenberg SA (2013) Treating B‑cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Nat Rev Clin Oncol 10:267–276. CrossRefPubMedGoogle Scholar
  20. 20.
    Kranz LM, Diken M, Haas H et al (2016) Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 534:1–16. CrossRefGoogle Scholar
  21. 21.
    Krummel MF, Allison JP (1995) CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 182:459–465CrossRefGoogle Scholar
  22. 22.
    Larkin J, Chiarion-Sileni V, Gonzalez R et al (2015) Combined nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med 373:23–34. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Mantovani A (1978) Effects on in vitro tumor growth of murine macrophages isolated from sarcoma lines differing in immunogenicity and metastasizing capacity. Int J Cancer 22:741–746. CrossRefPubMedGoogle Scholar
  24. 24.
    Mantovani A, Marchesi F, Malesci A et al (2017) Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol 14:399–416. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Marin-Acevedo JA, Dholaria B, Soyano AE et al (2018) Next generation of immune checkpoint therapy in cancer: new developments and challenges. J Hematol Oncol 11:1–20. CrossRefGoogle Scholar
  26. 26.
    Mittendorf EA, Clifton GT, Holmes JP et al (2012) Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients: from US Military Cancer Institute Clinical Trials Group Study I‑01 and I‑02. Cancer 118:2594–2602. CrossRefPubMedGoogle Scholar
  27. 27.
    Noguchi M, Moriya F, Suekane S et al (2012) Phase II study of personalized peptide vaccination for castration-resistant prostate cancer patients who failed in docetaxel-based chemotherapy. Prostate 72:834–845. CrossRefPubMedGoogle Scholar
  28. 28.
    Noy R, Pollard JW (2014) Tumor-associated macrophages: from mechanisms to therapy. Immunity 41:49–61. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Ochoa MC, Minute L, Rodriguez I et al (2017) Antibody-dependent cell cytotoxicity: immunotherapy strategies enhancing effector NK cells. Immunol Cell Biol 95:347–355. CrossRefPubMedGoogle Scholar
  30. 30.
    Petrelli F, Cabiddu M, Coinu A et al (2015) Prognostic role of lactate dehydrogenase in solid tumors: a systematic review and meta-analysis of 76 studies. Acta Oncol 54:961–970. CrossRefPubMedGoogle Scholar
  31. 31.
    Qian B‑Z, Pollard JW (2010) Macrophage diversity enhances tumor progression and metastasis. Cell 141:39–51. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Rosenberg SA, Packard BS, Aebersold PM et al (1988) Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med 319:1676–1680. CrossRefPubMedGoogle Scholar
  33. 33.
    Sahin U, Derhovanessian E, Miller M et al (2017) Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature 547:1–19. CrossRefGoogle Scholar
  34. 34.
    Sakuishi K, Apetoh L, Sullivan JM et al (2010) Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med 207:2187–2194. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Sharma P, Allison JP (2015) The future of immune checkpoint therapy. Science 348:56–61. CrossRefGoogle Scholar
  36. 36.
    Topalian SL, Hodi FS, Brahmer JR et al (2012) Safety, activity, and immune correlates of anti–PD-1 antibody in cancer. N Engl J Med 366:2443–2454. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Vignali DAA, Collison LW, Workman CJ (2008) How regulatory T cells work. Nat Rev Immunol 8:523–532. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Walter S, Weinschenk T, Stenzl A et al (2012) Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med 18:1254–1261. CrossRefPubMedGoogle Scholar
  39. 39.
    Wargo JA, Cooper ZA, Flaherty KT (2014) Universes collide: combining immunotherapy with targeted therapy for cancer. Cancer Discov 4:1377–1386. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Weide B, Martens A, Hassel JC et al (2016) Baseline biomarkers for outcome of melanoma patients treated with pembrolizumab. Clin Cancer Res 22:5487–5496. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Woo S‑R, Corrales L, Gajewski TF (2015) Innate immune recognition of cancer. Annu Rev Immunol 33:445–474. CrossRefPubMedGoogle Scholar
  42. 42.
    Woo S‑R, Turnis ME, Goldberg MV et al (2012) Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T‑cell function to promote tumoral immune escape. Cancer Res 72:917–927. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.Institut für ImmunologieUniversitätsmedizin, Johannes Gutenberg-Universität MainzMainzDeutschland

Personalised recommendations