Revolutionizing cancer treatment with immunotherapy

Immunity & Cancer

Power of immunotherapy: an increasingly important strategy against cancer

The idea that tumors could be recognized and rejected by the immune system was initially proposed in the late 19th century upon the observation that rare spontaneous tumor regressions occurred following infections, which may result in general activation of the immune system.1

More recently, preclinical studies revealed that tumors express immunogenic antigens and that these antigens induce immune responses that are able to protect against subsequent tumor challenges.2 Patients with melanoma were demonstrated to have T cells with specific activity against melanoma cells, and these cells were shown to be able to cause cancer regression when stimulated outside the body and returned to the patient.3-5

Over the last few years it has been recognized that the immune system in many patients has the ability to respond to cancer, but is usually prevented from doing so by immune defenses present in cancer cells. Many researchers and companies are studying a variety of means to overcome these defenses and activate the immune system more powerfully against cancer cells. Proof of concept for cancer immunotherapeutics has been established with recent drug approvals for various immune checkpoint inhibitors for metastatic melanoma and certain forms of lung cancer.

Cancer defenses limit the effectiveness of the natural immune response

The current model of cancer immunology is that tumor cells are antigenic (capable of being recognized by the immune system) but are insufficiently immunogenic due to multiple tumor-induced mechanisms of immune suppression that prevent the development of meaningful immune responses.

Cancer immunotherapy is based on restoring the ability of the immune system to be activated and attack the tumor.

Immunosuppression is known to be present in patients with SCCHN, who are consistently found to have disordered immune function at the time of presentation. Although they have normal B-cell function, immunoglobulin levels, and complement systems, SCCHN patients have immunological deficiencies of T-cell anergy and defective monocyte/macrophage function.6,7

The cumulative result of the various immune defects and immunosuppressive mechanisms in SCCHN is8:

  • The tumor successfully subverts the antigen presentation component (ie, dendritic cells) and the responding T-cell component of immunization, even though the tumor displays and sheds antigens capable of inducing immunization and tumor rejection
  • The compromised cellular immune response is, therefore, incapable of inducing tumor rejection

SCCHN: squamous cell carcinoma of the head and neck.

References:

  1. Nauts HC. Cancer Surv. 1989;8(4):713-723.
  2. Van Pel A, Boon T. Proc Nat Acad Sci USA. 1982;79(15):4718-4722.
  3. Parmiani G et al. J Nat Cancer Inst. 1990;82(5):361-370.
  4. Rosenberg SA et al. J Nat Cancer Inst. 1994;86(15):1159-1166.
  5. Shen X et al. J Immunother. 2007;30(1):123-129.
  6. Hadden JW et al. Int J Immunopharmacol. 1995;17(10):821-828.
  7. Whiteside T. Curr Oncol Rep. 2001;3:46-55.
  8. Schilling B et al. PLoS One. 2013;8:e47234.