The mechanisms most-often implicated in driving the spontaneous regression of cancer are thought to be mediated by immune system activation (or reactivation). Sometimes the driving force is an acute intercurrent bacterial or viral infection. Initiated by the work of Dr Lloyd Old, the founder of modern cancer immunology, the US Food and Drug Administration (FDA) in 1990 approved the first bacterial immunotherapy, Bacillus Calmette-Guerin (BCG), for in situ bladder cancer. More recently the FDA approved T-Vec [talimogene laherparepvec], a viral vaccine used to evoke an immune response in patients with advanced melanoma.27-29 

The development of other viral and bacterial vectors is an active area of new drug development, with further success anticipated.30,31 The recent approval of checkpoint inhibitors against an array of cancers and chimeric antigen receptor (CAR)-T cell therapy are testimonies to the power of the immune system, when it awakes from its slumber, to simulate a process historically regarded as “miraculous.”32,33


Continue Reading

The immuno-editing theory proposed by Drs Robert Schreiber, Mark Smyth, and Lloyd Old has helped to refine medical understanding of spontaneous regression, which may be seen as the interplay of cancer undergoing incomplete elimination, equilibrium, and escape.34 Under ideal conditions the innate and adaptive elements of the immune system work in concert to eliminate the cancer (often imperfectly) with regulatory (CD4+) and cytotoxic (CD8+) T cells, dendritic (or antigen presenting cells), natural killer (NK) cells, and macrophages along with a host of immune-activating secreted proteins such as interferon gamma, interleukin 12, and tumor necrosis factor (TNF) all working in harmony. Spontaneous regression may in some cases be a manifestation of this dynamic process, and immunoediting fits well into observations that most cancers that undergo spontaneous regression recur, sometimes years later.

Related Articles

Another example of this phenomenon can be seen with the so-called abscopal (or out-of-field) effects of radiation therapy, which causes the immune system to mount a systemic response to distant metastases.35

I expect that in the future, as our understanding of cancer immunity matures, the fascinating phenomenon of spontaneous regression will help guide us towards developing the safest and most effective drugs — which may ultimately lead to effective control of this devastating disease.

References

  1. Pack GT. St. Peregrine, O.S.M.–the patron saint of cancer patients. CA Cancer J Clin. 1967;17(4):181-2.
  2. Jackson R. Saint Peregrine, O.S.M.–the patron saint of cancer patients. Can Med Assoc J. 1974; 111(8):824-7.
  3. Krone B, Kölmel KF, Grange JM. The biography of immune system and the control of cancer: from St Peregrine to contemporary vaccination strategies. BMC Cancer. 2014;14:595. doi: 10.1186/1471-2407-14-595
  4. Duffin J. Medical Miracles: Doctors, Saints, and Healing in the Modern World. Oxford: 2008.
  5. Pukel C. Immunotherapy in the twentieth century: William Coley and Lloyd J. Old. Cancer Therapy Advisor website. Published March 15, 2017.
  6. Rohdenburg GL. Fluctuations of the growth energy of malignant tumors in man with especial reference to spontaneous reference. Cancer Res. 1918;(3)2:193-225.
  7. Morton JJ, Morton JH. Cancer as a chronic disease. Ann Surg. 1953;(137):683.
  8. Everson TC, Cole WH. Spontaneous regression of cancer: preliminary report. Ann Surg. 1956;144(3):366-80.
  9. Barrett R, Morash B, Roback D, et al. FISH identifies a KAT6A/CREBBP fusion caused by a cryptic insertional t(8;16) in a case of a spontaneously remitting congenital acute myeloid leukemia with normal karyotype. Pediatr Blood Cancer. 2017;64(8). doi: 10.1002/pbc.26450
  10. D’Arena G, Guariglia R, Pietrantuono G, et al. More on spontaneous regression of chronic lymphocytic leukemia: two new cases and potential role of lamivudine in a further patient with advanced disease and hepatitis B virus infection. Leuk Lymphoma. 2014:55(8):1955-7. doi: 10.3109/10428194.2013.858151
  11. Udupa K, Philip A, Rajendranath R, Sagar T, Majhi U. Spontaneous regression of primary progressive Hodgkin’s lymphoma in a pediatric patient: a case report and review of literature. Hematol Oncol Stem Cell Ther. 2013;6(3-4):112-6. doi: 10.1016/j.hermonc.2013.06.004
  12. Takahashi T, Ikejiri F, Takami S, et al. Spontaneous regression of intravascular large b-cell lymphoma and apoptosis of lymphoma cells: a case report. J Clin Exp Hematop. 2015;55(3):151-6. doi: 10.3960/jstrt.55.151
  13. Ito E, Nakano S, Otsuka M, et al. Spontaneous breast cancer remission: a case report. Int J Surg Case Rep. 2016;25:132-6. doi: 10.1016/j.ijscr.2016.06.017
  14. Nakamura Y, Noguchi Y, Satoh, E et al. Spontaneous remission of a non-small cell lung cancer possibly caused by anti-NY-ESO-1 immunity. Lung Cancer. 2009:65(1):119-22. doi: 10.1016/j.lungcan.2008.12.020
  15. Kitai H, Sakakibara-Konishi J, Oizumi S, et al. Spontaneous regression of small cell lung cancer combined with cancer associated retinopathy. Lung Cancer. 2015;87(1):73-6. doi: 10.1016/j.lung ca.2014.10.015
  16. Balzer BL, Ulbright TM. Spontaneous regression of testicular germ cell tumors: an analysis of 42 cases. Am J Surg Path. 2006;30(7):858-65.
  17. Lee T, Guo Y, Vij S, Bansal R, Wong NC, Shayegan B. Case: spontaneous regression of post-radical prostatectomy prostate-specific antigen elevation without adjuvant therapy in a patient with lymph node metastasis. Can Urol Assoc J. 2017;11(7):E315-7. http://dx.doi.org/10.5489/cuaj.4324
  18. Katano A, Takenaka R, Okuma K, Yamashita H, Nakagawa K. Repeated episodes of spontaneous regression/progression of cervical adenocarcinoma after adjuvant chemoradiation therapy: a case report. J Med Case Rep. 2015;9:114.
  19. Parks AL, McWhirter RM, Evason K, Kelley RK. Cases of spontaneous tumor regression in hepatobiliary cancers: implications for immunotherapy? J Gastrointest Cancer. 2015;46(2):161-5. doi: 10.1007/s12029-015-9690-7
  20. Chida K, Nakanishi K, Shomura H, et al. Spontaneous regression of transverse colon cancer: a case report. Surg Case Rep. 2017;3:65. doi: 10.1186/s40792-017-0341-z
  21. Pang C, Sharma D, Sankar T. Spontaneous regression of Merkel cell carcinoma: a case report and review of the literature. Int J Surg Case Rep. 2015;7C104-8. doi: 10.1016/j.ijscr.2014.11.027
  22. Bonvalot S, Ternes N, Fiore M, et al. Spontaneous regression of primary abdominal wall desmoid tumors: more common than previously thought. Ann Surg Oncol. 2013;20(13);4096-102. doi: 10.1245/s10434-013-3197-x
  23. Miller CV, Cook IS, Jayaramachandran R, Tyers AG. Spontaneous regression of a conjunctival malignant melanoma. Orbit. 2014;33(2);139-41. doi: 10. 3109/01676830.2013.851708.
  24. Diede SJ. Spontaneous regression of metastatic cancer: learning from neuroblastoma. Nat Rev Cancer. 2014;14(2):71-2 doi: 10.1038/nrc3656
  25. Buder T, Deutsch A, Klink B, Voss-Bohme A. Model-based evaluation of spontaneous tumor regression in pilocytic astrocytoma. PLoS Comput Biol. 2015;11(12):e1004662. doi: 10.1371/journal.pcbi.1004662
  26. Murphy KA, James BR, Guan Y, Torry DS, Wilber A, Griffith TS. Exploiting natural anti-tumor immunity for metastatic renal cell carcinoma. Hum Vaccin Immunother. 2015;11(7):1612–16.
  27. Kucerova P, Cervinkova M. Spontaneous regression of tumour and the role of microbial infection – possibilities for cancer treatment. Anticancer Drugs. 2016;27(4):269-277.
  28. Jhawar SR, Thandoni A, Bommareddy PK, et al. Oncolytic viruses-natural and genetically engineered cancer immunotherapies. Front Oncol. 2017;7:202. doi: 10.3389/fonc.2017.00202
  29. Corrigan PA, Beaulieu C, Patel RB, Lowe DK. Talimogene laherparepvec: an oncolytic virus therapy for melanoma. Ann Pharmacother. 2017:51(6):675-81. doi: 10.1177/1060028017702654
  30. Lee CH. Engineering bacteria toward tumor targeting for cancer treatment: current state and perspectives. Appl Microbiol Biotechnol. 2012;93(2):517-23. doi: 10. 1007/s00253-011-3695-3
  31. Howells A, Marelli G, Lemoine NR, Wang Y. Oncolytic viruses-interaction of virus and tumor cells in the battle to eliminate cancer. Front Oncol. 2017;7:195. doi: 10.3389/fonc.2017.00195
  32. Geng Q, Jiao P, Jin P, Su G, Dong J, Yan B. PD-1/PD-L1 inhibitors for immuno-oncology: from antibodies to small molecules. Curr Pharm Des. 2017 Oct 4. doi: 10.2174/1381612823666171004120152 [Epub ahead of print]
  33. Wilkins O, Keeler AM, Flotte TR. CAR T-cell therapy: progress and prospects. Hum Gene Ther Methods. 2017;28(2):61-6. doi: 10.1089/hgtb.2016.153
  34. Schreiber RD, Old LJ, Smyth MJ. Cancer Immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331(6024):1565-70. doi: 10.1126/science.1203486
  35. Cong Y, Shen G, Wu S, Hao R. Abscopal regression following SABR for non-small-cell-lung cancer: a case report. Cancer Biol Ther. 2017;18(1):1-3. doi: 10.1080/15384047.2016.1264541