Immunosuppression and Human Malignancy

278 Pages·1990·2.949 MB·English

by  David Naor, Benjamin Y. Klein, Nora Tarcic, Jonathan S. Duke-Cohan (auth.)

Immunosuppression and Human Malignancy
Contemporary Immunology
Immunosuppression and Human M.alignancy. by David Naor,
Benjamin Y. Klein, Nora Tarcie, and Jonathan S.
Duke-Cohan
Clinical Cellular Immunology. Molecular and Therapeutic
Reviews, edited by Albert A. Luderer and Howard H.
WeetalJ
The Lymphokines: Biochemistry and Biological Activity,
edited by John W. Hadden and William E. Stewart II
Immunosuppression
and Human Malignancy
Foreword by
Marc Feldmann
By
David Naor, Benjamin Y. Klein,
Nora Tarcic,
and Jonathan S. Duke-Cohan
The Lautenberg Center for General
and Tumor Immunology
The Hebrew University, Jerusalem, Israel
~
Humana Press· Clifton, New Jersey
© 1989 The Humana Press Inc.
Softcover reprint of the hardcover 1s t edition 1989
Crescent Manor
PO Box 2148
Clifton, NJ 07015
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted in any
form or by any means, electronic, mechanical, photocopying, microfilming, recording, or
otherwise without permission from the Publisher.
Ubrary of Congress Cataloging-in-Publication Data
Immunosuppression and human malignancy / by David Naor .. [et al.] ;
foreword by Marc Feldmann.
p. cm. -- (Contemporary immunology)
Bibliography: p.
ISBN-13: 978-1-4612-8846-6 e-13: 978-1-4612-4496-7
DOl: 10.[007/978-[-46[2-4496-7
1. Cancer--Immunological aspects. 2. Immunossuppression.
3. Cancer cells. 4. Suppressor cells. I. Naor, David.
II. Series.
[DNI.J<\: 1. Immune Tolerance. 2. Killer Cells, Natural--immunology.
3. Neoplasms--immunology. 4. Suppressor Cells--immunology.
5. Suppressor Cells--physiology. QW 56813391
RC268.3.14629 1989
616.99'4079--dc20
DNI.J<\IDC 89-7474
for Library of Congress CIP
"We shall require a substantially new manner of thinking if man
kind is to survive"
Albert Einstein
Contents
Foreword ............................................................ xi
Introduction......................................................... 1
Induction of Suppressor Cells by Immunostimulants
1. Introduction ............................................... 5
2. Induction of Suppressor Cells by BCG ............ 6
3. Induction of Suppressor Cells by C. parvum
and Other Immunostimulants ....................... 11
4. Conclusions ............................................... 14
Control of Natural Killer Cells by Suppressor Cells
1. Introduction ............................................... 15
2. Activity of Anti-NK Suppressor Cells in
Normal Animals ......................................... 16
3. Activation of Anti-NK Suppressor Cells by
Irradiation or Treatment with Estrogen........... 19
4. Activation of Anti-NK Suppressor Cells by
External Stimulators..................................... 21
5. Activity of Anti-NK Suppressor Cells in TBH... 27
6. Mechanisms................................................ 29
7. Suppression or Artifact?... ........... ................. 32
8. Suppressor Cells Controlling NK-Cell Activity
in Human Beings......................................... 33
vii
viii Contents
Antigenic Entities of the Tumor That Induce
Suppressor Cells May Prevent the Potentiation of
Coexpressed Immunogenic Entities......................... 41
Suppressor Cells in Human Malignant Diseases
1. Introduction ............................................... 55
2. Hodgkin's Disease ...................................... 59
3. Non-Hodgkin's Lymphomas, Leukemias,
and Multiple Myelomas ............................... 74
3.1. Introduction......................................... 74
3.2. Non-Hodgkin's Lymphoma ........ ............ 76
3.3. Acute Lymphoblastic Leukemia .............. 80
3.4. Chronic Lymphocytic Leukemia .............. 86
3.5. Chronic Myelogenous Leukemia ............. 98
3.6. Human T Cell Lines with Suppressor-Cell
Characteristics ...................................... 99
3.7. Multiple Myeloma ....... ............... .... ....... 99
4. Cancer of the Head and Neck ....................... 103
5. Lung Cancer .............................................. 112
6. Alimentary-Tract Malignancies ...................... 121
7. Genitourinary Malignancies .......................... 127
8. Gynecologic Malignancies ............................ 129
9. Cancer of the Breast .................................... 130
10. Melanoma and Other Skin Malignancies ........ 133
11. Malignancies of the Central Nervous System .. 141
12. Some Considerations of the Role of Immune
Suppression in Human Malignancy ............... 142
13. The Effect of Antineoplastic Chemotherapy
on Human Suppressor-Cell Activity............... 162
Suppressor Cells and Malignancy in Animal Experimental
Models: A Brief Summary of Recent Findings
1. Suppressor Macrophages and "Null" Cells . .... 165
2. "Sneaking Through" of Low Doses of Tumor
Cells Is Mediated by Suppressor Cells ........ .... 166
3. Suppressor T Cells and Their Mechanism
of Action ................................................... 167
4. Suppressor T Cell Lines and Clones .............. 172
Contents ix
5. Suppression of Concomitant Immunity.... ...... 173
6. Immunotherapy Based on Suppressor Cells
Eradication ...... ........ ..... ....... ....... ........ ....... 174
7. Immunoregulation of Antitumor
Autoimmunity by Suppressor T Cells ............ 177
General Conclusions ............................................. 181
References ............. ........ ........ ......... .... ....... ... ... .... 189
Appendix ............................................................ 261
Index .................................................................. 265
Foreword
The immune system can deal effectively with the majority of
viruses and bacteria, less effectively with parasites, and very
poorly with cancer. Why is this so? Why are McFarlane Burnet's
and Lewis Thomas' predictions that the immune system is in
volved in ridding the body of cancer cells, encapsulated in the
catchy phrase "immunologic surveillance," so difficult to experi
mentally establish?
Cancer differs from infectious agents in being derived from
the host. Hence, it has been postulated that cancer cells lack anti
gens that the immune system can recognize. They are not "im
munogenic." However, this argument is seriously weakened by
the existence of numerous human autoimmune diseases, in
which the immune system effectively recognizes and attacks a va
riety of self tissues. Thus, the potential clearly exists for recogni
tion of the surfaces of tumor cells.
Professor Naor and his colleagues have written a book that
explores another possible reason: cancer cells are recognized by
the immune system-but is it possible that the consequence of
recognition is inhibition of the immune system-by suppressor T
cells or macrophages? The evolution of the malignant state may
only occur in individuals who develop this suppression.
This book reviews the evidence that suppressor cells, poorly
characterized and difficult to study, may be of fundamental im
portance in cancer. In fact, our incapacity to understand the na
ture of suppressor cells and their mode of action is one of the ma
jor problems in immunology research today.
Clearly, further work is needed in this area to complete the
analysis of suppressor phenomena in cancer, and the book by
Prof. Naor and his colleagues will greatly assist all those who
wish to push their explorations more deeply into its intricacies.
Marc Feldmann
The Charing Cross Sunley Research Centre
Hammersmith, London, UK
xi
Introduction
If one reviews the literature dealing with the function of
suppressor macro phages and suppressor T cells in experimental
animals confronted with malignancy (1,2), one may reach a con
clusion that increased suppressor-cell function is frequently asso
ciated with the immunodepression observed in many tumor
bearing hosts (TBH). It is difficult, however, to evaluate the
genuine extent of immunodepression in experimental models of
malignancy, and its relationship to concurrent suppressor cell
function, simply because negative results are not always
reported.
A separate question is how much the immunodepression
mediated by suppressor cells is associated with the initial trans
formation event of malignancy and with the promotion of tumor
growth. Again, it is impossible to make any generalization: at one
extreme, we may observe in animals tumor progression despite
normal immunocompetence (3-5), and at the other extreme,
there is clear evidence that immunodepression mediated by sup
pressor cells is associated with the progression of cancer or even
with the carcinogenic process itself (1,2). These latter experimen
tal models further imply that the immune system may control tu
mor progression, if excessively active suppressor cells do not in
terfere. Indeed, our previous review articles (1,2) present many
examples of experimental cancer prevention, or even therapy,
that were dependent on the eradication of suppressor cells and
the subsequent establishment of an efficient immune response
against the tumors.
In order to assess the association of suppressor cells with the
human malignant process, one must first demonstrate the exis
tence of increased suppressor-cell activity in patients with malig
nant diseases and, secondly, must correlate the function of the
suppressor cells with the immunocompetence and the patholog
ical status (stage of disease, remission, or relapse) of the patients.
From experimental models, we have learned that suppressor-cell
function presented in vitro does not necessarily indicate a general
depression of the immune response (4). Even if an association be-
1