William Bradley Coley, MD, and the phenomenon of spontaneous regression

Abstract

The standard definition of spontaneous regression (SR) of cancer is as follows, “…when a malignant tumor partially or completely disappears without treatment or in the presence of therapy which is considered inadequate to exert a significant influence on neoplastic disease.” SR is also known as Saint Peregrine tumor, the name taken from a young priest, Peregrine Laziosi (1260 [5]–1345, exact date is unknown), who had been diagnosed with a tumor of the tibia. The mass eventually grew so large that it broke through the skin and became severely infected. The available treatment for this condition was limited to amputation. Historical records report that on the day of surgery, physicians found that the tumor had disappeared and reportedly never returned. To date, the medical literature consists only of individual case studies and overviews of this phenomenon. The most cited work on the subject was done by surgeons Tilden Everson and Warren Cole who reviewed 176 published cases of SR from 1900 to 1960. While a percentage of these were found not to be cases of SR, there remained a number of unexplained cases. A frequent theme in many cases of SR is the co-occurrence of infection. Given the current interest in immunotherapy in the treatment of cancer, this article discusses one of the very early pioneers of this theory, William Bradley Coley, MD, a surgeon who was clearly ahead of his time. Ostracized by colleagues for his belief that stimulation of the immune system could in fact produce a regression of cancer, Coley remained convinced that his theory was right and, while he was not familiar with cytokines such as tumor necrosis factor (TNF), interferons, and streptokinase, he knew instinctively that an innate immune response was taking place.

Macrophage Origin, Metabolic Reprogramming and IL-1β Signaling: Promises and Pitfalls in Lung Cancer

“…As discussed above the relationship between inflammation and cancer is complicated, probably driven by an immunosuppression within TME. However, the concept of immunotherapy came from Coley’s observation that cancer regression can be achieved by active bacterial infection [208,209]. Thus, the higher incidence of bacterial infection in the CANTOS trial [210] may suggest that by dampening chronic low-grade inflammation, canakinumab has unlocked an unspecific bacterial lung antitumoral activity.…”

Bispecific T-Cell Redirection versus Chimeric Antigen Receptor (CAR)-T Cells as Approaches to Kill Cancer Cells

“…Years later, upon researching Stein’s case, cancer physician William Coley became convinced that the bacterial infection led to a response against the tumor [2,3]. Coley then systematically treated some of his own cancer patients with live bacteria in efforts to stimulate their immune response against the tumors [1,2,3]. These studies yielded variable results but with some clear clinical successes, particularly against sarcomas.…”

Managing Metastatic Thymoma With Metabolic and Medical Therapy: A Case Report

“…First, it is possible that immune activation contributed to both regressions. So-called "spontaneous" regressions have been documented for thousands of years in a variety of cancers (29). The mechanism of spontaneous regression remains unknown but may involve the activation of antigen recognition mechanisms such that the immune system becomes capable of recognizing cancer cells, allowing for the establishment of active immunity against tumors (30).…”