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This Week’s Citation CIassic~______
rcocir.. A J. SplIg W G S. Macisle ~ M & Thom C E. Postoperative depression of
tumour-directed cell-mediated immunity in patients with malignant disease.
Med. J. 4:67-70, 1972.
[I Bs*.
University Departments of Pathology and Dermatology. Western Infirmary. Glasgow. Scotland]
Cell-mediated immunity to tumor-associated antigens
was measured betore and after surgery (leukocvte migratlon inhibition test) in 1 2 patients with breast carcinoma and 12 with malignant melanoma. Postoperatively leukocyte migration inhibition was reduced in
all patients or a period from 6 to 22 days. [The SCIe
indicates that this paper has been cited in over 205
publications.)
p
Surgery.~elatedImmune Suppression
in Cancer Patients
21,
plausible explanations of the article’s popularity.
by the p~~~dky
thattumor ~op-e.onn
might relate to invnune suppression, we went on to
eaanuine many facets of the inuseume response in patients with cancer at various stages of progression.
1q88
This study developed from investigations
1 of factors
predictive of outcome for melanoma. Prognosis
could be estimated with iadidantlal accuracy, using
a multlfactoiial dlinicopathological score sheet.
However, it was clear that factors other than those
detectable by clinical inspection and microscopy
wale inspu.t.it. One factor that was considered eelevant was the role of the immune system in twoplasia. The late 1%Os was a period of great activity
in tumor immunology and the Karolineka’s Dspastmeat of Tienor lilology, with George Klein and Eva
Klein, was a mecca to miring tumor invnunologiit,.
Two years spent there imprinted a firm conviction
that inumine factors ate important in human cancer
and should most propedy be studied in man.
Sack inGlasgow adecision wasmade to studycelkilar invnwsity in melanoma(because ofbroad hints
from the clinic that this wan an imnwnogenic tumor)
and breast cancer (because of its frequency and ire.
quendy fatal outcome). A highly esithusiastic team
formed: Sousa at. MacIde, lecturer in dermatology
with an interest in ,nslanocytlc tumors; Walter G.S.
Splig., lecturer in pathology, ~
it
tal pathology: and Catherine E. Thomas, a biology
doctoral student interested in woddng with human
material. Thés was a democratic gioup in w4,lch all
were involved in study design, acquisition of materiak, and benchwo,k (thoogh Katie did most
ea,.ri...ents).
— —
conclusively proved or disproved. Thatthis was one
of the earliest convincing demonstratiom of postoperative inususese suppression and continuing concern
that tide mmd may facilItate msttasee ate the most
Alistair J. Cochran
partments of Pathology and Surgery
School of Medicine
University of California
Los Angeles, CA t0024-1732
September
The
it.~.,t were to demonstrate cellular immialty toHanor’deflvsd materials in vibu and to shetennine whelfier siullar results were obtained in Ion.
gitvdissal studies of individual patients. They were
not, and this tsispsred spirited discussions of eaper~
insental technique until it was recognized that the
apparent inconsistencies were related In time to the
—.
Further esperiments
co.4lnwed tramiient isuuuwie suppression following
surgery, possibly caused by the metabolic consequencesof surgery and the effect, of anesthetic and
other dn~This raised concenis that this window
of inunune suppression nllgbt facilitate the establishrnen( of tianor cell, disseminated during surgical
manipulation. Such a poseibhllly is hard to study in
humans and, despite its importance, has yet to be
We found that general immune competence was
maintained in most patients until their disease
advanced
2 and they were subject to multisystem
failure.
The team dissolved amicably in the late 1970s,
MacIde becoming professor of dermatology at the
University of Glasgow, Spilg becoming consultant
p.thiM~Mat the Victoria hdlnnary in Glasgow, and
Thomas, having obtained her PhD, mar,~lngand giving Isp science, at least for a time. I moved to Los
Angeles to jern other devotee, of melanoma inusnuisology at the University of California, Los Angeles.
Madde, in Glasgow, continues to work on a wide
r~ of aspects of melanoma, contributing to World
Health Organization clinical studies of the value of
ruonspeci& therapeutic immune stimulation and
EO(TC studies of the specificity and sensitivity
of a wide range of antimelanoma monoclonal
Since coming to Los Angeles I have again become
interested in the 0 .b4efll. of immune
suppression
35
and cancer. In a series of papera, we have shown
that the tysugilu node, nearest to melanoma are
)mmune-ipppressed, contain abundant presssppressot cells, and permit the survival of small manthers
of tumor cells. We save also shown that met,noma-derived products, such as gangliosides, prostaglasidhtue, and metibrane llpoprotelns, can downregulate lymph node cells.’ We consider that local
immune suppression induced by tumor products facilitates the survival of tumor cells and their espan.
non into nietastaaee. live occurs in patients who are
generally inwnuowcowpetent.
t. Co~sn A J. Meelod for assessment of prognosis in malignant melanoma. Lan~2: t062-4, 1968. (Cited 35 times.)
2. Cautran A J. MwàIe B 98. Greet B 98, Ross C K. C~ M D. S_~k~ G. W~ey K. Itoyle D K &
Jackaa. A 98. Enaminacion of immunology of calmer patinas. mt. i Cancer 18:298-309, 976. (Cited 45 times.)
3. Hose D S I. Kors K I & Cac&rss A J. Vorrationsllunctional asmuim competence of human tumor-draining lymph nodes.
Cancer Rca. 47:1740-4. 987.
4. Ileon I) $ B, Meeter B & Cost,.. A J. Suppressor cell activity a metanoma-draimng lymph nodes.
Cancer Ret. 47:1529-33, 1987.
5. Coder.. A j. We. O-& & Morton D I. Occult melanoma cells In mite lymph aides of patients with pathological Stage I
malignant melanoma. Amer. I. Swg. PsiIioI. 12:612-S. 988.
6. Hoes 0 SB, lets B F & Co~.n A J. Ganglionides from haitian mnelanomas mmanomoduiate the response of T cells to
,nterisukin-2. Cell Immunol. 8:410-9. 1988.
CURRENT CONTENTS~
~1989by ISII!I
LS, V. 32. #2. Jan. 9. 1989
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