Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

More documents

Recommendations

Info

7 Immunosuppresive Factors in Cancer Richard Bucala and Christine N. Metz 7.1 Introduction Tumors have paradoxical effects on the host immune system: they stimulate immune cells and they suppress immune cells. When host immunostimulation is effective, tumor cells are destroyed. However, tumors produce several suppressive cytokines and other factors that subvert the host antitumor immune response. These immunosuppressive factors function by repressing the host antitumor immune cells and/or by promoting host immunosuppressor cell activity. Suppression of the host antitumor immune response occurs by preventing tumor recognition by immune cells and/or by inhibiting immune cell-mediated tumor killing. An accurate identification and understanding of the immunosuppressive factors that contribute to the host antitumor immune response is critical for the effective treatment of cancer patients, whether by conventional treatments or by newly developed immunotherapeutic strategies. In this chapter, we will discuss the effects of tumor-derived suppressive cytokines, factors, and shed antigens on host immune cells (summarized in Tab. 7.1) and on tumor cells. In addition, we will address the implications for the inhibition of these immunosuppressive agents during cancer treatment. 7.1 Transforming Growth Factor (TGF)-b Cancer Immune Therapie: Current and Future Strategies Edited by G. Stuhler and P. Walden Copyright # 2002 Wiley-VCH Verlag GmbH & Co. KGaA ISBNs: 3-527-30441-X (Hardback); 3-527-60079-5 (Electronic) TGF-b was originally described for its ability to induce NRK rat kidney fibroblasts to form large colonies in soft agar in the presence of epidermal growth factor [1, 2]. Since its discovery, TGF-b has been shown to play a role in cell growth, differentiation and transformation, and to modulate the host immune response to tumor growth and metastases. The TGF-b superfamily consists of TGF-b1, -b2 and -b3, as well as an additional 40 different TGF-b-related proteins (reviewed in [3]). The three mammalian isoforms (TGF-b1, -2 and -3) are synthesized as pre-pro-TGF-b polypeptides that contain a signal sequence, the pro-region [latency associated peptide (LAP)] and mature TGF-b (N-terminal region). The majority of TGF-b is secreted as an inactive complex associated with a second gene product known as the ªlatent 119
Tab. 7.1 Effects of tumor-derived molecules on the host antitumor immune response Factor Monocytes/macrophages Dendritic cells T lymphocytes Natural killer cells (NK)/ lymphokine activated killer (LAK) TGF-b ; mac production ; cytokine and NO production ; mac proliferation `deactivates` macs IL-10 ; cytokine synthesis by macs ; PGE2 production ; NO production by macs ; MHC class II exprn ; co-stimulatory molecule exprn MIF ; macrophage migration associated with : mac activation : COX-2/PGE2 production ; DC maturation ; DC activity alters DC chemotaxis ; DC ability to stimulate T cell responses ; DC migration ; DC accumulation alters DC maturation ; DC apoptosis ; T cell lytic activity ; Th1 cytokine release ; T cell proliferation ; T cell differentiation ;/: T cell apoptosis indirect and direct effects ; Th1 cytokine production ; AG-induced CD4 + proliferation ;/: T cell cytolytic responses induces CD4 + T cell anergy :/; CTL activity : CD8 + T cell proliferation : CD8 + T cell outgrowth indirect and direct effects mediates T cell activation ; presence of intra-tumoral T cells associated with ; CTL activity ; NK cytokine production ; NK proliferation ; NK cytolytic activity ; LAK production ; LAK cytotoxic activity : IL-2 induced NK proliferation : NK cytokine production : NK cytotoxicity ; NK activity : TNF production by macs : T cell proliferation ; NK activity PGE2 ; antitumor activity of macs ; Th1 cytokine production ; T cell migration ; T cell activation ; CTL generation/activity : T cell anergy ; LAK activity Polyamines ; NO production by macs ; cytokine production by macs ; mac phagocytosis Shed tumor antigen: MUC See text for details and references. required for CTL induction required for T cell differentiation ; effectiveness of CTL response ; T cell proliferation ; cytokine production by T cells ; T cell activation ; NK activity 120 7 Immunosuppresive Factors in Cancer
Page 1 and 2:
Cancer Immune Therapie: Current and
Page 3 and 4:
Editors: Dr. Gernot Stuhler Univers
Page 5 and 6:
VI Preface Recent years have seen a
Page 7 and 8:
VIII Contents 2.5.3 Antigens Encode
Page 9 and 10:
X Contents 6.4.2 Natural Killer (NK
Page 11 and 12:
XII Contents 9.6 Loading DC with An
Page 13 and 14:
XIV Contents 14.2.2.1 Cancer-specif
Page 15 and 16:
List of Contributors Richard Bucala
Page 17 and 18:
Color Plates Fig. 5.2 The MHC class
Page 19 and 20:
Fig. 5.5 Different immune effector
Page 21 and 22:
Fig. 5.17 Possible pathway for the
Page 23 and 24:
Fig. 6.2 T lymphocytes in the tumor
Page 25 and 26:
Index a acidic and basic fibroblast
Page 27 and 28:
±, see also tumors cationic lipids
Page 29 and 30:
e EBV see Epstein-Barr virus EDR se
Page 31 and 32:
immature Mo-DCs 184 immune cells ±
Page 33 and 34:
MHC class I antigen-processing mach
Page 35 and 36:
±, onco- 209 ±, over-expressed ce
Page 37 and 38:
TICD see tumor-induced cell death T
Page 39 and 40:
Part 1 Tumor Antigenicity Cancer Im
Page 41 and 42:
4 1 Search for Universal Tumor-Asso
Page 43 and 44:
Page 45 and 46:
Page 47 and 48:
10 1 Search for Universal Tumor-Ass
Page 49 and 50:
Page 51 and 52:
Page 53 and 54:
Page 55 and 56:
18 2 Serological Determinants On Tu
Page 57 and 58:
Page 59 and 60:
Page 61 and 62:
Page 63 and 64:
Page 65 and 66:
Page 67 and 68:
30 Cancer Immune Therapie: Current
Page 69 and 70:
32 3 Processing and Presentation of
Page 71 and 72:
Page 73 and 74:
Page 75 and 76:
Page 77 and 78:
Page 79 and 80:
42 4 T Cells In Tumor Immunity cult
Page 81 and 82:
44 4 T Cells In Tumor Immunity cell
Page 83 and 84:
46 4 T Cells In Tumor Immunity to T
Page 85 and 86:
48 4 T Cells In Tumor Immunity Alth
Page 87 and 88:
50 4 T Cells In Tumor Immunity Tab.
Page 89 and 90:
52 4 T Cells In Tumor Immunity rest
Page 91 and 92:
54 4 T Cells In Tumor Immunity 53 T
Page 93 and 94:
Part 2 Immune Evasion and Suppressi
Page 95 and 96:
60 5 Major Histocompatibility Compl
Page 97 and 98:
Page 99 and 100:
Page 101 and 102:
Page 103 and 104: 68 Tab. 5.1 HLA class I loss attrib
Page 105 and 106: 70 5 Major Histocompatibility Compl
Page 131 and 132: 96 6 Immune Cells in the Tumor Micr
Page 133 and 134: 98 6 Immune Cells in the Tumor Micr
Page 135 and 136: 100 6 Immune Cells in the Tumor Mic
Page 153: 118 6 Immune Cells in the Tumor Mic
Page 157 and 158: 122 7 Immunosuppresive Factors in C
Page 191 and 192: 156 8 Interleukin-10 in Cancer Immu
Page 205 and 206:
170 8 Interleukin-10 in Cancer Immu
Page 207 and 208:
Page 209 and 210:
Page 211 and 212:
Part 3 Strategies for Cancer Immuno
Page 213 and 214:
180 9 Dendritic Cells and Cancer: P
Page 215 and 216:
Page 217 and 218:
Page 219 and 220:
Page 221 and 222:
Page 223 and 224:
Page 225 and 226:
Page 227 and 228:
Page 229 and 230:
Page 231 and 232:
Page 233 and 234:
Page 235 and 236:
Page 237 and 238:
Page 239 and 240:
206 10 The Immune System in Cancer:
Page 241 and 242:
Page 243 and 244:
Page 245 and 246:
Page 247 and 248:
Page 249 and 250:
Page 251 and 252:
Page 253 and 254:
Page 255 and 256:
Page 257 and 258:
Page 259 and 260:
Page 261 and 262:
Page 263 and 264:
Page 265 and 266:
232 11 Hybrid Cell Vaccination for
Page 267 and 268:
Page 269 and 270:
Page 271 and 272:
Page 273 and 274:
Page 275 and 276:
Page 277 and 278:
Page 279 and 280:
Page 281 and 282:
Page 283 and 284:
Page 285 and 286:
Page 287 and 288:
254 12 Principles and Strategies Em
Page 289 and 290:
Page 291 and 292:
Page 293 and 294:
Page 295 and 296:
Page 297 and 298:
Page 299 and 300:
Page 301 and 302:
Page 303 and 304:
270 13 Applications of CpG Motifs f
Page 305 and 306:
Page 307 and 308:
Page 309 and 310:
Page 311 and 312:
Page 313 and 314:
Page 315 and 316:
Page 317 and 318:
Page 319 and 320:
Page 321 and 322:
288 14 The T-Body Approach: Towards
Page 323 and 324:
Page 325 and 326:
Page 327 and 328:
Page 329 and 330:
Page 331 and 332:
Page 333 and 334:
300 15 Bone Marrow Transplantation
Page 335 and 336:
Page 337 and 338:
Page 339 and 340:
Page 341 and 342:
Page 343 and 344:
Page 345 and 346:
312 16 Immunocytokines: Versatile M
Page 347 and 348:
Page 349 and 350:
Page 351 and 352:
Page 353 and 354:
Page 355 and 356:
Page 357 and 358:
Page 359 and 360:
Page 361 and 362:
Page 363 and 364:
Page 365 and 366:
Page 367 and 368:
Page 369 and 370:
Page 371 and 372:
Page 373 and 374:
Page 375 and 376:
Page 377 and 378:
Page 379 and 380:
Page 381 and 382:
348 17 Immunotoxins and Recombinant
Page 383 and 384:
Page 385 and 386:
Page 387 and 388:
Page 389 and 390:
Page 391 and 392:
Page 393 and 394:
Page 395 and 396:
Page 397 and 398:
Page 399 and 400:
Page 401 and 402:
Page 403 and 404:
Page 405 and 406:
Page 407 and 408:
Page 409 and 410:
Page 411 and 412:
Page 413 and 414:
Page 415 and 416:
382 Glossary tion to the variable d
Page 417 and 418:
384 Glossary suppressor gene produc
Page 419 and 420:
386 Glossary press the proper recep
Page 421 and 422:
388 Glossary gp96 See Chaperone. Gr
Page 423 and 424:
390 Glossary cytes and addressing l
Page 425 and 426:
392 Glossary T bodies are being tes
show all

Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?