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Hellstróm K E & HellstTöm I. Lymphocyte-mediated cytotoxicity and blocking
serum activity to tumor antigens. Advan. Immunol. 18:209-77, 1974.
[Depts. Pathology, Microbiology, and Immunology, Univ. Washington
Medical School, Seattle, WA]
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This paper reviews evidence that lym- tumor cells from the donors of the respecphocytes from animals and human patients tive sera and they disappeared shortly after
with tumor are specifically reactive to cells tumor removal. In 1971, we obtained evifrom the same tumor in vitro and that their dence that the circulating blocking factors
reactivity can be prevented by circulating were circulating antigen-antibody com‘blocking factors’ such as tumor antigens plexes and that free antigen
could also serve
and antigen-antibody complexes. (The SCI® as a blocking factor.2
indicates that this paper has been cited a
“The findings that we had obtained were
total of 653 times of which 8 occurred in confirmed
and extended in other laborato1974, 74 in 1975, 119 in 1976, 113 in 1977, ries.3 They contradicted the prevailing view
126 in 1978,87 in 1979,66 in 1980, and 60 in that lymphocyte clones that are reactive to
1981.]
a given tumor antigen are absent (‘forbidden’) from the tumor-bearing host. They inp
—
dicated, instead, that lymphocyte reactivity
be regulated, and we proposed that
Karl Erik Hellstrdm and Ingegerd Hellstrbm must
the ‘blocking factors’ play an intricate part
Fred Hutchinson Cancer Research Center
in this regulation. Further evidence supportUniversity of Washington
ing the view of regulation of lymphocyte ac1124 Columbia Street
tivity rather than clonal loss came from
Seattle, WA 98104
studies which we performed on rats that had
been made tolerant to skin allografts. These
January 25, 1982
rats had lymphocytes that were reactive in
“In 1966, we both started working at the
vitro to the tolerated tissue, and they also
University of Washington Medical School in
had circulating
4 blocking factors, inhibiting
Seattle, having left George Klein’s group at
this reactivity.
the Karolinska Institute in Stockholm,
“Our 1974 paper in Advances in Immunolwhere we got our training. The project on
ogy reviewed the5e findings. We believe
which we embarked concerned lymphocyte
that the reason our paper has been much
reactivity to tumor-associated antigens as
cited reflects both the great amount of inassayed in vitro.
terest and the considerable controversy
“We found, rather to our surprise, that
which our rather unexpected observations
lymphocytes from mice with growing, chem- caused. Today, it is generally accepted that
ically induced sarcomas were often as reac- reactive lymphocytes occur in tumor-beartive to cells from the same sarcomas in vitro
ing animals, that their activity is subject to
as were lymphocytes from mice whose
close regulation, that blocking factors in the
tumors had been removed. Similar findings
form of tumor antigens and complexes turn
were made with other experimentally in- on suppressor T cells, and that other block5
duced tumors and with human neoplasms.
ing factors are the products of such cells.
“In an attempt to learn why tumors can
The greatest advancement since 1973 is that
grow progressively in vivo, in spite of the
it has become possible, using proper cell surfact that the tumor-bearing individuals’ lym- face markers, to dissect subsets of lymphocytes can kill plated tumor cells in vitro,
phocytes with distinct functions, while in
we tested serum from the respective tumor1974 we did not know of NK cells and of
bearers for any adverse effect on the ability
various types of T killer, helper, and supof the lymphocytes to react. We observed
pressor cells. Thus, the phenomenological
that tumor-bearer serum could suppress
framework in which we and others were
(‘block’) lymphocyte reactivity, and we at- then working is gradually being replaced by
tributed this to circulating ‘specific blocking
knowledge at the cellular and even at the
factors.’l These factors were able to bind to
molecular level.”
1. Hefletrom I, Hellatröm K K, Evans CA, Heppaer G, Piece. G E ~ Yang I PS. Serum mediated protection
of neoplastic cells from inhibition by lymphocytes immune to their tumor specific antigens.
Proc. Nat. Aced. Sci. ifS 62:362-9, 1969.
2. SJngren H 0, Heflutrons I, B.nsal S C & Hellsuöm K K. Suggesting evidence that the ‘blocking antibodies’ of tumorbearing individuals may be antigen-antibody complexes. Proc. Nat. A cad. Sci. US 68:1372-5, 1971.
3. BaldwIn H W, Price M R & Robins H A.Inhibition of hepatoma-isnmune lymph node cell cytotoxicity by
tumor-bearer serum, and solubilized hepatonsa antigen. fin. I. Cancer 11:527-35, 1973.
4. Bawal S C, Heilsinun K E, Heflstshm I & Sjiigiea H 0. Cell-mediated Immunity and blocking Serum
activity to tolerated allografts in rats. I. Erp. Mcd. 137:590-602, 1973.
5. Heflstrom K E £ Brown I P. Tumor antigens. (Sela M, ed.) The antigens.
New York: Academic Press, 1979. Vol. 5.p. 1-82.
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