Immunotherapy in Oncology

  • Paolo Andrea ZucaliEmail author


The immune system has been recognized to interact with cancer for more than a century. According to the hypothesis of the immune surveillance, the immune system could be able to recognize and reject cancer cells as being foreign exactly in the same way that it fights transplanted organs and microbial agents. If in oncology traditional therapies, such as chemotherapy, kinase inhibitors, surgery, and radiation therapy, directly target cancer cells, immunotherapy indirectly fights the tumor by the activation of antitumor immunity. In the last years, immunotherapy is found to be an effective therapeutic strategy in several cancers. Despite the clinical success of antibodies against the immune regulators such as the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), the programmed death receptor 1 (PD-1), or its ligand (PD-L1), unfortunately only a part of patients with cancer exhibit durable response, suggesting that a deeper knowledge of cancer immunity is needed. The definition of immune profiles able to predict responses to immunotherapy is also a crucial unmet need.


Immunotherapy Checkpoint inhibitors Anti-PD-1 Anti-PD-L1 Anti-CTLA4 Cancer treatment 


  1. 1.
    Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3:991–8.CrossRefGoogle Scholar
  2. 2.
    Boon T, Cerottini JC, Van den Eynde B, van der Bruggen P, Van Pel A. Tumor antigens recognized by T lymphocytes. Annu Rev Immunol. 1994;12:337–65.CrossRefGoogle Scholar
  3. 3.
    Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1–10.CrossRefGoogle Scholar
  4. 4.
    Brassard DL, Grace MJ, Bordens RW. Interferon-α as an immunotherapeutic protein. J Leukoc Biol. 2002;70:565–81.Google Scholar
  5. 5.
    Golomb HM, Jacobs A, Fefer A, et al. Alpha-2 interferon therapy of hairy-cell leukemia: a multicenter study of 64 patients. J Clin Oncol. 1986;4:900–5.CrossRefGoogle Scholar
  6. 6.
    Kirkwood JM, Butterfield LH, Tarhini AA, Zarour H, Kalinski P, Ferrone S. Immunotherapy of cancer in 2012. CA Cancer J Clin. 2012;62:309–35.CrossRefGoogle Scholar
  7. 7.
    Redelman-Sidi G, Glickman MS, Bochner BH. The mechanism of BCG therapy for bladder cancer: a current perspective. Nat Rev Urol. 2014;11:153–62.CrossRefGoogle Scholar
  8. 8.
    Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271:1734–6.CrossRefGoogle Scholar
  9. 9.
    Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.CrossRefGoogle Scholar
  10. 10.
    Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–54.CrossRefGoogle Scholar
  11. 11.
    Allen PB, Gordon LI. PD-1 blockade in Hodgkin’s lymphoma: learning new tricks from an old teacher. Expert Rev Hematol. 2016;9:939–49.CrossRefGoogle Scholar
  12. 12.
    Beckermann KE, Johnson DB, Sosman JA. PD-1/PD-L1 blockade in renal cell cancer. Expert Rev Clin Immunol. 2017;13:77–84.CrossRefGoogle Scholar
  13. 13.
    Beckermann KE, Jolly PC, Kim JY, Bordeaux J, Puzanov I, Rathmell WK, Johnson DB. Clinical and immunologic correlates of response to PD-1 blockade in a patient with metastatic renal medullary carcinoma. J Immunother Cancer. 2017;5:1.CrossRefGoogle Scholar
  14. 14.
    Garon EB. Current perspectives in immunotherapy for non small cell lung cancer. Semin Oncol. 2015;42(Suppl 2):S11–S8.CrossRefGoogle Scholar
  15. 15.
    Garon EB. Selecting patients for immune checkpoint inhibition in lung cancer. Clin Adv Hematol Oncol. 2015;13:490–2.PubMedGoogle Scholar
  16. 16.
    Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, et al. Pembrolizumab versus ipilimumab in advanced melanoma. N Engl J Med. 2015;372:2521–32.CrossRefGoogle Scholar
  17. 17.
    Sonpavde G. PD-1 and PD-L1 inhibitors as salvage therapy for urothelial carcinoma. N Engl J Med. 2017;376:1073–4.CrossRefGoogle Scholar
  18. 18.
    Gaillard SL, Secord AA, Monk B. The role of immune checkpoint inhibition in the treatment of ovarian cancer. Gynecol Oncol Res Pract. 2016;24:11.CrossRefGoogle Scholar
  19. 19.
    Khanna S, Thomas A, Abate-Daga D, Zhang J, Morrow B, Steinberg SM, Orlandi A, Ferroni P, Schlom J, Guadagni F, et al. Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab. J Thorac Oncol. 2016;11:1993–2005.CrossRefGoogle Scholar
  20. 20.
    Lordick F, Shitara K, Janjigian YY. New agents on the horizon in gastric cancer. Ann Oncol. 2017;28:1767–75.CrossRefGoogle Scholar
  21. 21.
    Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27:450–61.CrossRefGoogle Scholar
  22. 22.
    Pulluri B, Kumar A, Shaheen M, Jeter J, Sundararajan S. Tumor microenvironment changes leading to resistance of immune checkpoint inhibitors in metastatic melanoma and strategies to overcome resistance. Pharmacol Res. 2017;123:95–102.CrossRefGoogle Scholar
  23. 23.
    Chen C, Chen Z, Chen D, Zhang B, Wang Z, Le H. Suppressive effects of gemcitabine plus cisplatin chemotherapy on regulatory T cells in non small-cell lung cancer. J Int Med Res. 2015;43:180–7.CrossRefGoogle Scholar
  24. 24.
    Ghiringhelli F, Menard C, Puig PE, Ladoire S, Roux S, Martin F, Solary E, Le Cesne A, Zitvogel L, Chauffert B. Metronomic cyclophosphamide regimen selectively depletes CD4+ CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother. 2007;56:641–8.CrossRefGoogle Scholar
  25. 25.
    Vacchelli E, Ma Y, Baracco EE, Sistigu A, Enot DP, Pietrocola F, Yang H, Adjemian S, Chaba K, Semeraro M, et al. Chemotherapy-induced antitumor immunity requires for mylpeptide receptor 1. Science. 2015;350:972–8.CrossRefGoogle Scholar
  26. 26.
    Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–20.CrossRefGoogle Scholar
  27. 27.
    Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology: mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348:124–8.CrossRefGoogle Scholar
  28. 28.
    Topolian SZ. Targeting immune checkpoints in cancer therapy. JAMA. 2017;318:1647–8.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Medical OncologyHumanitas Clinical and Research Hospital—IRCCSRozzanoItaly

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