Conventional wisdom long held that the human immune
system was no match for cancer. Born of na- tive cells,
the logic went, cancer fooled the immune system into
concluding it was harmless. Thus protected from attack,
cancer easily thrived until its host died.
A deeper understanding of our bio-
logical defenses has changed that. The
human immune system does battle
cancer. But we could better optimize
our defenses to fend off malignant dis-
ease. That’s clear from cancer treat-
ments attempted in New York City
and Germany as early as the 19th
century. Those experiments and other
undervalued evidence from the medi-
cal literature suggest that acute infec-
tion -- in contrast to chronic infection,
which sometimes causes cancer -- can
help a body fight tumors.
It’s not the pathogens that do the
good work. But the way our bodies
respond to the pathogens is key. Infec-
tion events, especially those that pro-
duce fever, appear to shift the innate
human immune system into higher
gear. That ultimately improves the per-
formance of crucial biological machin-
ery in the adaptive immune system.
This lesson comes, partly, from doctors
who risked making patients sicker to
try to make them better.
Toxin Therapy
Elisabeth Dashiell was 17 when she
entered New York Hospital in the
autumn of 1890 with severe pain in
her hand but no sign of infection. Her
newly trained surgeon, William B.
Coley, saw no improvement after a pe-
riod of observation. In November 1890,
a biopsy revealed round-cell sarcoma,
a relatively rare form of cancer origi-
nating in soft tissue and bone.
Shortly after the biopsy, Dashiell’s
arm was amputated below her elbow,
but her cancer still spread ferociously.
In December a tumor was detected in
her right breast; within days, nodules
appeared in her left breast. By January
a huge tumor swelled in her abdomen
and her heart began to fail. On January
23, 1891, Dashiell died.
Medicine back then offered little
more than amputation and morphine
to cancer patients such as Dashiell.
Shocked by his ineffectiveness, Col-
ey dove into hospital records and the
medical literature for clues to how to
help more. He found about 90 sarcoma
case reports. About half contained fol-
low-up histories. The one that grabbed
him most involved Fred Stein.
Stein, a German immigrant, had
been diagnosed with cheek sarcoma in
1884. Despite four operations, his can-
cer kept recurring. He was considered
a hopeless case. However, in late 1884
Stein developed high fever from ery-
sipelas, a post-operative skin disease
common in that era. To the great sur-
prise of his physicians, his tumor dis-
appeared. Stein was discharged from
the hospital in February 1885.
Five months after Elisabeth Dashiell
died, Coley tracked Stein to New York
City’s Lower East Side. Photographed
and examined, Stein showed no trace of
residual cancer six years after his puz-
zling recovery. That drove Coley to dig
deeper for records of similar cases. The
young doctor, who had studied some
German at Yale University, likely en-
countered a report published more than
two decades earlier, in 1868, in the jour-
nal Berliner Klinische Wochenschrift.
The German physician F. Busch re-
ported that he had observed a patient’s
tumor “re-absorbed” after a high fever.
Unconstrained by modern ethics rules,
Busch tested for some connection him-
self. That summer, by coincidence, a
patient with a mild erysipelas infec-
tion that followed an injury and a 19-
year-old girl with a huge sarcoma of
the neck entered Busch’s clinic around
the same time. Over five months, the
sarcoma had grown to the size of a
child’s head. His patient’s breathing
was threatened; she could not com-
pletely close one eye.
Before antibiotics, erysipelas was
one of the leading causes of death from
postoperative infections in hospitals.
Still, Busch burned a small piece of skin
over the girl’s tumor and attached a cot-
ton pad taken from the erysipelas pa-
tient onto her wound. The surrounding
skin developed signs of erysipelas and
the patient developed a high fever -- 104
degrees Fahrenheit. Her tumor, which
had been tight and dense, softened and
shrank rapidly. Within two weeks it
reached the size of a small apple. She
could close her eyes and breathe freely.
Unfortunately, the young lady devel-
oped circulatory problems and steps
had to be taken to strengthen her weak
condition. With the disappearance
of the skin inflammation, the tumor
reached its prior size. She left the clinic
with an unknown fate.
Healing Heat: Harnessing Infection
to Fight Cancer
Modern immunology plus historic experiments suggest a better way
to gear up the human immune system to battle malignant disease
By Uwe Hobohm
Uwe Hobohm is cell biologist and professor of
bioinformatics at the University of Applied Sci-
ences in Giessen, Germany. He received his Ph.D.
from the University of Bremen. He has worked at
the European Molecular Biology Laboratory in
Heidelberg and at F. Hoffmann-La Roche in Basel.
He is the author of two books on cancer intended
for popular audiences and has published scientific
articles in cell biology, bioinformatics and immu-
nology. Address: University of Applied Sciences
Giessen, Bioinformatics, Wiesenstrasse 14,
D-35390, Giessen, Germany. Internet:
http://bio-info.tg.fh-giessen.de/cancer
In his literature search, Coley found
more than 40 cases of disappearance
of malignancies during an erysipelas
attack. He came across another medi-
cal pioneer, Friedrich Fehleisen, also in
Germany, who was the first to use cul-
tured bacteria in related experiments.
After successes and failures, Fehleisen
discontinued the work. Still, Coley de-
cided to try for himself.
In April 1891 an Italian immigrant,
Mr. Zola, presented at New York Hos-
pital with a large sarcoma tumor in his
neck and an egg-sized metastasis in his
right tonsil. He had been operated on
twice before but was in hopeless condi-
tion. He could hardly speak or swallow
and was unable to eat solid food. His
life expectancy was, at the very most, a
few months. By all known means, there
was nothing to lose.
Since erysipelas was so hazardous,
the hospital was reluctant to host Col-
ey’s experiment, so it was performed in
a private apartment. Colleagues at the
College of Physicians and Surgeons,
now part of Columbia University, pre-
pared the bacteria. Three applications
were delivered over three weeks, with
minor success. Zola’s temperature rose
only slightly and he showed no sign of
full-blown infection. Coley tried a fresh
preparation and a larger dose. Within
hours, Zola developed severe chills,
headache and vomiting. His temper-
ature did not reach what one could
expect from a full-blown erysipelas in-
fection; it did not exceed 102 degrees
Fahrenheit. But the tumor diminished
in size, as did the tonsil tumor. About
one month after the treatment began,
Zola could eat again.
Via a friend, Coley obtained fresh
and potent bacteria culture from the
leading German bacteriologist, Rob-
ert Koch. That fall, he again treated
Zola, whose temperature that time
rose above 104 degrees with nausea,
vomiting and severe pain. The infec-
tion almost killed him but, within
two weeks, the neck tumor was not
observable. The tonsil tumor stopped
growing. Zola was in excellent health
when Coley saw him four years later
in October.
During the following two years
Coley attempted to infect 12 patients
who had inoperable cancer. He failed
to induce a full-blown infection in four
and succeeded in eight. All eight re-
sponded. Six had partial tumor remis-
sions. Two showed full remission. But
two patients died from infection. So
Figure 1. A fibrous dendritic cell scans the surface of a lymphocyte, a vital step in the cascade of events that alerts a body’s immune system to
a biological threat and prompts a customized attack. Clues from medicine’s past and growing insights into our complex immune system may
one day bolster people’s natural defenses against cancer.
Olivier Schwartz, Institute Pasteur/Science Photo Library, Nature
Coley abandoned living cultures and
turned toward what today we would
call a bacterial extract.
Refining a Method
Coley tried inactivated microbes on
four patients but obtained only modest
fever-inducing effects and temporary
changes in their tumors. The prepara-
tions likely were too weak. By the end
of 1892, the French doctor G. H. Roger
had published his observation that the
virulence of the erysipelas bacterium,
Streptococcus pyogenes, increased when
it was grown in the presence of anoth-
er, then called Bacillus prodigiosus, now
Serratia marcescens, a mild pathogen in-
volved in eye and urinary infections.
In January 1893 Coley administered
for the first time one variant of what
today are still called “Coley’s toxins.” It
was a heat-sterilized, combined culture
of S. pyogenes and S. marcescens bacteria
administered by injection. The patient
was a 16-year-old boy with a large in-
operable abdominal tumor, a malignant
sarcoma. After receiving increasing dos-
es over 10 weeks, the boy developed
symptoms mimicking those of a heavy
erysipelas infection: chills, headache,
fever, local redness and swelling at in-
jection sites. The tumor shrank by 80
percent. Coley kept in touch with his
patient, who remained cancer free for
more than 20 years.
Coley treated another five patients
during 1893. No result was as prom-
ising as his first. Coley published the
results of his experiments in the The
American Journal of the Medical Sciences
under the title “The treatment of malig-
nant tumors by repeated inoculations of
erysipelas: with a report of ten original
cases” in 1893. The report stirred con-
siderable excitement -- for a while.
At the beginning of the 20th
century
radiation treatment came on the can-
cer therapy scene. This new procedure
captured nearly the full attention of
the oncology community due to its im-
mediately visible effects. One could
now, it seemed, x ray away tumors.
Within the medical mainstream, inter-
est in Coley’s methods faded.
Still, some physicians did try to test
Coley’s treatment. Nicholas Senn of
Rush Medical College in Chicago re-
ported uniform failure of the method.
William Keen, a surgeon in Phila-
delphia, failed to obtain a response
in seven patients. A Dr. Caulkins of
Watertown, New York, reported a
large number of successes, as did Dr.
Matagne from Belgium, who prepared
his own fresh extracts. Matagne pub-
lished his observations in lower-tier
French and Belgian journals.
Two stubborn surgeons, S. L. Chris-
tian and L. A. Palmer, at the U.S. Ma-
rine Hospital in Stapleton, New York,
reported a spectacular cure in 1928.
Two years before, a U.S. Marine cap-
tain they described as “G. B.” devel-
oped bone sarcoma and endured an
above-the-knee amputation. He was
31. In 1926, G. B. received daily injec-
tions of “Coley’s fluid” from January
5 to February 20, until he seemed too
weak to endure more. Treatments were
started and stopped that spring and
started again that summer, fall and
Figure 2. Dr. William B. Coley holds his young daughter, Helen, on his lap. As an adult, Helen
Coley-Nauts championed her father’s pioneering efforts in cancer immunology. She also
founded the Cancer Research Institute in New York, which today awards millions of dollars
in research grants annually. Photo courtesy of the Cancer Research Institute.
winter, with daily injections totaling 20
weeks cumulatively. The patient was
last examined on January 9, 1928. No
evidence of disease was present.
Coley, throughout his 40-plus-year
career, treated hundreds with mul-
tiple versions of his toxin. He never
achieved a clear-cut, uniform result.
Some patients responded. Among
them, some were cured but some were
not. At a 1934 meeting, Coley dis-
cussed 44 cases of Ewing’s sarcoma.
Twelve out of 44 patients had been
treated with radiation by other physi-
cians and none of these survived five
years. But the remaining 32 patients
had been treated with bacterial extract
by Coley. Twelve of them remained
disease free for more than five years.
A five-year survival rate of zero after
radiation and 38 percent after Coley’s
treatments merited deeper scrutiny.
Helen Coley-Nauts, Coley’s daugh-
ter, meticulously re-examined her fa-
ther’s clinical cases after his death. This
was not easy. Undoubtedly a man of de-
termination, Coley was not a methodi-
cal scientist. His patient records were a
mess, he treated different patients for
different time periods and his bacterial
extracts, over time, were inconsistently
made. Coley-Nauts counted 15 differ-
ent preparations. Eleven of them, she
concluded, were not potent enough to
have a strong effect.
Coley-Nauts determined that her
father had treated several hundred
patients by the time he died in 1936,
many of whom had received radiation
and sometimes surgery as well. To esti-
mate the overall success of extracts, the
analysis should be restricted to patients
with inoperable cancer and treated by
toxin alone. In another review from
1994, immunologist and oncology re-
searcher Charles Starnes identified 170
such patients with adequate medical
records (121 with some form of sarco-
ma, 43 with carcinoma and myeloma,
and 6 with melanoma). The remission
rate among them was 64 percent; the
five-year survival rate was more than
44 percent.
According to the Coley-Nauts and
Starnes analyses, treatment success cor-
related with length of therapy and the
fevers induced by the toxins. Higher
was better. This correlation was report-
ed among several other observations
but without emphasis or any explana-
tion by the authors.
Only a few uncoordinated attempts
to apply Coley’s ideas were pursued
from mid-century on. Bacterial ex-
tracts used in the later studies, in the
1960s and 1970s, were commercial
preparations called MBV (produced
by Bayer) or Vaccineurin (produced by
Suedpharma of Munich). They were
similar to, but not identical to, Coley’s
extracts. The experimenters appeared
to be hunting for anti-cancerous sub-
stances that could be applied a limited
number of times to work, a traditional
cancer therapy model embraced by
pharmaceutical companies. Length
of treatment and fever level were not
adequately considered. A majority of
the patients in the studies had been
pretreated by chemotherapy, radiation
or both, measures that likely distorted
the immune response that appears to
be triggered by the bacterial extracts.
Results were mixed: several remis-
sions, even long lasting ones, with sev-
eral failures.
Well-controlled studies of bacte-
rial-extract cancer treatment that in-
corporate all the lessons from the
retrospective analysis of Coley’s and
other treatments have not been pur-
sued since. But medical case studies,
cancer epidemiology and our more
precise understanding of immunology
make a strong case that they should.
Spontaneous regression or remission
is the partial or complete disappear-
ance of an untreated malignant tumor
or a tumor treated with a therapy con-
sidered inadequate to exert significant
influence. It sounds like fantasy, but
about 1,000 case studies in the medical
literature during the past century de-
tail spontaneous regression from can-
cer. Surely more have occurred. And
there’s a pattern to some of the cases.
A prior fever was recorded in 25
to 80 percent of documented cases of
spontaneous regression of cancer. For
instance, Diamond and Luhby in 1951
reported 26 spontaneous remissions in
a cohort of 300 cases of childhood leu-
kemia; 80 percent were accompanied
by infection. Stephenson et al. in 1971
investigated 224 cases of spontaneous
regression and reported that in 62 cases,
or 28 percent, regression was preceded
by either an infection or a persistent
temperature elevation. In many cases,
S. pyogenes, the pathogen that produced
erysipelas, was involved.
Harnessing Immunity
It is not true, as Coley believed of S.
pyogenes, that all these pathogens pro-
duce some cagey anti-cancerous sub-
stance. Even malaria was reported in
the case histories -- a disease caused by
plasmodia rather than a virus or bac-
terium. It’s unlikely that pathogens of
such disparate evolutionary roots could
produce the same cancer fighter. Much
more likely is that the sequence of im-
mune reactions triggered by the infec-
tions was the same.
The immune system is capable of
finding malignant cell, just as it is
able to localize a bacterium, a virus,
a worm or a malaria plasmodium. As
early as 1956, scientists observed that
the survival rates of gastric cancer pa-
tients correlated with the number of a
specific type of immune cell observed
in and around their tumors. The more
tumor infiltrating lymphocytes (TIL),
the better. Still, millions of people die
from cancer each year. Why?
Barriers must exist to prevent an or-
ganism’s immune system from attack-
ing its own tissue. Otherwise, devas-
tating autoimmune diseases would be
more common. Mammalian immune
systems are structured to maintain a
delicate balance between recognition
and removal of pathogens and not at-
tacking “self.” Bacteria and viruses are
invaders that the immune system gen-
erally is poised to attack. Malignant
cells, derived from native cells, don’t
generate the same reaction since they
are “self” -- at least that was the long
held explanation.
Cancer cells can carry hundreds of
mutations that distinguish them from
healthy cells. But the immune system
often remains in an “observer” state
Figure 3. When the patient known today only
as Mr. Zola met Coley in New York, he suf-
fered from a disfiguring neck sarcoma. Photo
courtesy of the Cancer Research Institute.38 American Scientist, Volume 97
in their presence rather than engaging
in battle as it does against bacterial or
viral infections. The reason for this in-
complete immune response is a long-
standing puzzle in cancer immunology.
William Coley’s experiments may help
today’s scientists solve it.
The human immune system can be
broadly divided into two parts, the
innate and the adaptive. The older,
innate immune system reacts within
minutes after invading pathogens are
encountered. The adaptive system,
which employs evolutionarily younger
and more customized tools, takes lon-
ger to generate specialized antibodies
and T cells to attack threats.
A look into vaccinology illustrates
why involvement of the innate system
may be crucial. Ordinary vaccines like
those against measles, smallpox, tu-
berculosis or whooping cough either
contain “attenuated” live pathogens,
sterilized pathogens or pathogenic an-
tigens. These components are geared
toward the adaptive immune system;
they lead to the production of patho-
gen-specific antibodies or T cells.
But all vaccines contain another
component, so-called adjuvants. For
decades nobody understood why ad-
juvants enhance the immune reaction.
The immunologist Charles Janeway
called adjuvants “doctors’ dirty little
secret.” Today we know that adjuvants
stimulate the underestimated portion
of the immune system, the innate arm.
Some vaccines would be almost use-
less without an adjuvant.
Evolution wired both arms of our
immune response to work together. A
defective innate system allows patho-
gens to attack more rapidly, putting the
slower adaptive system at risk of being
overrun. For too long, the attention in
cancer immunology was focused on
the adaptive part of the immune sys-
tem alone. Only in recent years have
cancer immunologists turned their at-
tention to understanding the role of
the innate system.
Scientists have expanded the obser-
vation from the 1950s that a high num-
ber of lymphocytes near gastric tumor
tissue improves patient survival. The
same pattern has been found in more
than 3,400 patients with cancer of the
breast, bladder, colon, prostate, ovary,
rectum and brain. In the case of breast
cancer, the difference was striking. Pa-
tients with high numbers of TIL had a
six-year survival rate of more than 60
percent, whereas no patients with very
low numbers survived. P. H. Cugnenc
et al. observed in 2006 that the location
and density of T cells within colorectal
tumors is a better predictor of patient
survival than tumor classification by
size and spread. This is a profound ob-
servation, since it proves that the im-
mune system keeps can constrain can-
cer, at least for a while.
In these cases, presumably, constant
elimination of some malignant tissue
takes place, although not complete
eradication. At the same time tumor
cells evolve due to their inherent ge-
netic instability. They produce variants
leading to successive cell populations
with different immunogenicity -- dif-
ferent vulnerability. Thus, while one
variant cell is detected and destroyed,
another variant develops for which the
immune system has to generate novel
bullets. The outcome is often fatal.
Dendritic cells, which link the innate
and adaptive immune systems, likely
are hugely important players in re-
straining cancer. Dendritic cells act like
patrolling sentries, prowling bound-
aries between the body and the outer
world on and under skin, within the
epidermis and within mucous mem-
branes in the mouth, nose, ear and co-
lon. These cells ingest pathogens and
cell debris and produce from them
structures known as antigens -- biologi-
cal fingerprints that stimulate T cells
and B cells to customize their immune
attacks. Dendritic cells carry those anti-
gens to lymph nodes and display them
on their surfaces to T cells, key actors in
the molecular chain that launches adap-
tive immune attacks.
There is one important requirement
in this scenario that has not been rec-
ognized until recently. Dendritic cells
need so-called danger signals to be-
come maximally activated. Cancer
cells do not produce the right signals
to activate them; but certain classes
of bacterial and viral components do.
They are called pathogen-associated
molecular patterns (PAMP).
PAMP is the name for a collection of
chemically diverse substances found
in parts of biological invaders such
as the lipopolysaccaride in bacterial
cell walls or the flagellin in bacterial
propellers. PAMP also exists includes
double-stranded RNA found in virus-
es and parts of infectious fungi, such
as mannan or zymosan. They bind to
the same protein family in the human
body as do adjuvants in vaccines: so-
called Toll-like receptors (TLR), which
dendritic cells employ. No other class
of substances is known to induce mat-
uration of dendritic cells as efficiently
as PAMP. That ability may explain
how bacterial infection, in the presence
Figure 4. Toll-like receptors (TLR) on dendritic cell surfaces bind with PAMP elements from
invading pathogens. TLR signals reach the cell nucleus where cytokine genes get turned on,
enabling full activation of dendritic cells. Activation allows dendritic cells to carry specific
alarms to the immune apparatus. There are multiple TLR types in humans.
of fever, can mobilize immune attacks
against cancer.
The details of this hypothesized
cross-immune stimulation are not yet
known. But a hint may be distilled from
an experiment published in 2004. Can-
cers are known to tone down immune
responses. They produce and release
immune-suppressing signals into their
environment, phenomena called tumor
escape or tumor tolerance induction.
Drew Pardoll at Johns Hopkins Univer-
sity and colleagues wanted to break this
tolerance and revitalize a normal im-
mune response against an established
tumor in mice. His group administered
dendritic cells plus tumor antigen, but
tolerance for the antigen remained.
In a second experiment, dendritic
cells were infected with a virus. Now,
tolerance for the cancer antigen was
broken and the immune system,
pushed into a higher gear, launched a
full attack. This makes sense. Viruses
produce PAMP. Dendritic cells are ful-
ly activated with help from PAMP.
This suggests an explanation for Col-
ey’s success with some of his patients
and for those documented spontaneous
cancer remissions after fevers. Dendritic
cells ingest both pathogens and dying
cells and eventually display antigens
needed to activate T cells, probably by
displaying both on their surface. And
it’s likely that fever has an important
role in this scenario. As Klemens Trieb
et al. reported back in 1994, cancer cells
can be more vulnerable to heat than nor-
mal cells. Fever produces heat, so it is
fair to argue that fever may produce an
unusually high amount of cell debris
from cancer cells, possibly resulting in
potentially more cancer-cell antigens be-
ing collected by dendritic cells. The im-
mune system requires a certain amount
of antigen for full activation; low antigen
levels are ignored.
Fever As Weapon
But fever is not recognized as a thera-
peutic tool in clinical settings. In fact,
fever is a nuisance to patients and
staff. Fever accompanies dangerous
infections, so its removal is equated
with removing danger. A proliferative
infection can cause circulatory prob-
lems and patients experiencing them
need to be monitored closely. Multiple
incentives persist to use an aspirin or
another antipyretic to shut it down.
But fever induced by sterilized path-
ogens or pathogenic substances is much
less dangerous than a proliferative in-
fection. Circulatory problems caused
by Vaccineurin, a fever-inducing drug
containing Streptococcus extracts used
in German private clinics until the early
1990s, were extremely rare. These fevers
usually lasted less than a day and then
declined automatically.
Some clinical tests using PAMP have
been pursued in recent years. That
comes from the recognition that PAMP
represents a novel group of substances
that could be patented for profit. How-
ever, experiments involving PAMP have
been guided by magic-bullet thinking
favored by pharmaceutical companies.
Important lessons from Coley and his
contemporaries, including those related
to fever, are not being adequately incor-
porated in the testing. Fever usually is
suppressed as an adverse reaction dur-
ing the tests. But that is not all.
PAMP therapies usually are tested
in patients who have had prior che-
motherapy, radiation therapy or both.
These patients have compromised im-
mune systems. Optimal results can only
Figure 5. Activated, mature dendritic cells are needed to activate T cells and induce a full-
blown immune response. Dendrtitic cells need antigens from cell debris and pathogens,
particularly PAMP, to fully activate. Fever may increase the amount of cancer-cell debris that
dendritic cells encounter, improving the chances of specialized attacks on cancer cells.
What the Literature Says
Within the immense, international cancer literature, multiple publications observe that infections appear to be associated with
lower cancer risk later in life and to increase the odds of cancer regression. This observation does not hold for chronic infec -
tions, which can actually induce cancers. Only six of the more recent studies included age-adjusted controls.
Clockwise from upper left: 1941 poster promoting early syphilis treatment; patient in Illinois
tuberculosis camp, 1908; 1938 poster promoting early cancer diagnosis and treatment; trans-
mission electron microscopy (TEM) image of Herpes simplex virions; chest x-ray revealing a
fibrothorax due to previous empyema; TEM image of Hepatitis B virions; TEM image of sin-
gle measles virion; Red Cross demonstration during 1918 influenza pandemic; blast crisis of
chronic myelogenous leukemia; and malaria remedies advertised on a South Carolina shack
in 1938. Full references can be found under http://bioinfo.tg.fh-giessen.de/cancer. (All images
courtesy of the Library of Congress or the Centers for Disease Control and Prevention.)
be expected in patients with noncom-
promised immune systems. Also, in
contrast to a natural infection, where a
mixture of PAMP molecules invades a
host, only single substances are tested
in the clinical trials. That’s the case even
though vaccine research has taught
us that living attenuated or sterilized
pathogens induce a much stronger im-
mune response than single antigens.
Single PAMP, in general, will induce a
much weaker immune response than
would bacterial extracts.
When cancer worsens, PAMP treat-
ment is stopped. But we know from
Coley-era experiments that benefits
sometimes take a long time to material-
ize. Instead, a fixed and not too small
number of treatments should be pur-
sued without interruption. The goal of
such trials is to cure, which is admirable.
But we know from other immunothera-
peutic trials that sometimes a stabiliza-
tion of the disease occurs, where ma-
lignant foci do not disappear, but stop
growing. Stabilization of disease should
become an additional goal.
PAMP treatments are applied intra-
venously. But we have hints that stimu-
lators of the innate immune system can
be much more powerful when they are
applied where the antigen is, namely
close to the tumor. And in the present
studies, PAMP doses are applied only
a few times. It is likely that the innate
immune system, lacking memory, must
be stimulated again and again.
A different approach is in order. Mul-
tiple types of PAMP should be combined
into a cocktail. PAMP should be injected
close to tumors. If surgery is required, it
might be advisable to start PAMP thera-
py before surgery, when antigen load is
high, and continue it afterward to eradi-
cate residual neoplasm. Fever should be
allowed, if not stimulated.
On the Internet today, Coley’s toxins
are celebrated as an unjustly ignored
therapy ready and able to cure cancers.
Such simplicity is a vast overstatement
since Coley himself had very mixed re-
sults. But we have much to learn from
his experiments, from the suggestive
epidemiology and from the records
of spontaneous regressions. It is time
to integrate what they teach with our
improved understanding of the innate
immune system. Otherwise, the full
potential of PAMP therapy will not be
leveraged.
There may be prophylactic potential
here as well. Epidemiological studies
suggest that a personal history that
includes several infections with fever
sometimes significantly reduces the
likelihood a person will develop cancer
later (see What the Literature Says). One
potential explanation is that feverish
infections reduce would-be malignant
cells. If that’s true, the implications are
profound.
Antibiotics must be applied immedi-
ately for life-threatening diseases such
as lung infection or tuberculosis. But we
must ask: Should we apply antibiotics
and antipyretics (fever lowering drugs)
early and for all minor infections? If we
do not, more people will endure un-
pleasant days in bed. But quick allevia-
tion of discomfort should be weighed
carefully against the potential loss of
long-term benefit.
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