b8ec673de60dec7161e9a4c15399afc9 236083.pdf b7cfe3970a040db891154390c33b2a4989f03a74 236083.pdf e00ec9b186aa77d2f3962ad9f0a59d16a8e2c2affd53197251dcdfb45efc4802 236083.pdf Title: Immune-Checkpoint Inhibitors in B-Cell Lymphoma Subject: For years, immunotherapy has been considered a viable and attractive treatment option for patients with cancer. Among the immunotherapy arsenal, the targeting of intratumoral immune cells by immune-checkpoint inhibitory agents has recently revolutionised the treatment of several subtypes of tumours. These approaches, aimed at restoring an effective antitumour immunity, rapidly reached the market thanks to the simultaneous identification of inhibitory signals that dampen an effective antitumor response in a large variety of neoplastic cells and the clinical development of monoclonal antibodies targeting checkpoint receptors. Leading therapies in solid tumours are mainly focused on the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) pathways. These approaches have found a promising testing ground in both Hodgkin lymphoma and non-Hodgkin lymphoma, mainly because, in these diseases, the malignant cells interact with the immune system and commonly provide signals that regulate immune function. Although several trials have already demonstrated evidence of therapeutic activity with some checkpoint inhibitors in lymphoma, many of the immunologic lessons learned from solid tumours may not directly translate to lymphoid malignancies. In this sense, the mechanisms of effective antitumor responses are different between the different lymphoma subtypes, while the reasons for this substantial difference remain partially unknown. This review will discuss the current advances of immune-checkpoint blockade therapies in B-cell lymphoma and build a projection of how the field may evolve in the near future. In particular, we will analyse the current strategies being evaluated both preclinically and clinically, with the aim of fostering the use of immune-checkpoint inhibitors in lymphoma, including combination approaches with chemotherapeutics, biological agents and/or different immunologic therapies. Keywords: immune checkpoint; lymphoid neoplasms; programmed death 1; cytotoxic T-lymphocyte antigen 4; monoclonal antibodies; combination therapies Author: Marc Armengol, Juliana Carvalho Santos, Miranda Fernández-Serrano, Núria Profitós-Pelejà, Marcelo Lima Ribeiro and Gaël Roué Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Jan 19 08:45:11 2021 CET ModDate: Tue Jan 19 09:44:43 2021 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 43 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2290511 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- YWSFCB+VnURWPalladioL Type 1 Custom yes yes no 10 0 ZTRHGD+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 IEBMSS+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 LDTLQC+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 IUYWSY+VnURWPalladioL-Bold Type 1 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Perspectives Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@74ad1f1f Info: Title: Immune-Checkpoint Inhibitors in B-Cell Lymphoma Author: Marc Armengol, Juliana Carvalho Santos, Miranda Fernández-Serrano, Núria Profitós-Pelejà, Marcelo Lima Ribeiro and Gaël Roué Subject: For years, immunotherapy has been considered a viable and attractive treatment option for patients with cancer. Among the immunotherapy arsenal, the targeting of intratumoral immune cells by immune-checkpoint inhibitory agents has recently revolutionised the treatment of several subtypes of tumours. These approaches, aimed at restoring an effective antitumour immunity, rapidly reached the market thanks to the simultaneous identification of inhibitory signals that dampen an effective antitumor response in a large variety of neoplastic cells and the clinical development of monoclonal antibodies targeting checkpoint receptors. Leading therapies in solid tumours are mainly focused on the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) pathways. These approaches have found a promising testing ground in both Hodgkin lymphoma and non-Hodgkin lymphoma, mainly because, in these diseases, the malignant cells interact with the immune system and commonly provide signals that regulate immune function. Although several trials have already demonstrated evidence of therapeutic activity with some checkpoint inhibitors in lymphoma, many of the immunologic lessons learned from solid tumours may not directly translate to lymphoid malignancies. In this sense, the mechanisms of effective antitumor responses are different between the different lymphoma subtypes, while the reasons for this substantial difference remain partially unknown. This review will discuss the current advances of immune-checkpoint blockade therapies in B-cell lymphoma and build a projection of how the field may evolve in the near future. In particular, we will analyse the current strategies being evaluated both preclinically and clinically, with the aim of fostering the use of immune-checkpoint inhibitors in lymphoma, including combination approaches with chemotherapeutics, biological agents and/or different immunologic therapies. 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709 Annotation: Subtype: Link Rect: 182, 675, 220, 686 Annotation: Subtype: Link Rect: 59, 641, 97, 651 Annotation: Subtype: Link Rect: 222, 606, 260, 617 Annotation: Subtype: Link Rect: 516, 583, 553, 594 Annotation: Subtype: Link Rect: 104, 549, 142, 559 Annotation: Subtype: Link Rect: 429, 514, 466, 525 Annotation: Subtype: Link Rect: 472, 514, 509, 525 Annotation: Subtype: Link Rect: 207, 479, 244, 490 Annotation: Subtype: Link Rect: 251, 479, 287, 490 Annotation: Subtype: Link Rect: 118, 446, 155, 456 Annotation: Subtype: Link Rect: 162, 446, 198, 456 Annotation: Subtype: Link Rect: 167, 388, 204, 398 Annotation: Subtype: Link Rect: 211, 388, 247, 398 Annotation: Subtype: Link Rect: 59, 342, 97, 352 Annotation: Subtype: Link Rect: 103, 342, 139, 352 Annotation: Subtype: Link Rect: 259, 307, 297, 318 Annotation: Subtype: Link Rect: 303, 307, 339, 318 Annotation: Subtype: Link Rect: 86, 273, 124, 283 Annotation: Subtype: Link Rect: 275, 249, 313, 260 Annotation: Subtype: Link Rect: 446, 226, 484, 237 Annotation: Subtype: Link Rect: 337, 192, 374, 203 Annotation: Subtype: Link Rect: 59, 169, 97, 180 Annotation: Subtype: Link Rect: 103, 169, 139, 180 Annotation: Subtype: Link Rect: 136, 135, 173, 145 Annotation: Subtype: Link Rect: 179, 135, 216, 145 Annotation: Subtype: Link Rect: 520, 111, 557, 122 Annotation: Subtype: Link Rect: 59, 100, 95, 111 Annotation: Subtype: Link Rect: 279, 65, 316, 76 Annotation: Subtype: Link Rect: 322, 65, 359, 76 Page: Sequence: 35 Annotations: Annotation: Subtype: Link Rect: 402, 709, 440, 720 Annotation: Subtype: Link Rect: 168, 525, 205, 536 Annotation: Subtype: Link Rect: 402, 491, 439, 502 Annotation: Subtype: Link Rect: 287, 364, 324, 375 Annotation: Subtype: Link Rect: 264, 330, 302, 341 Annotation: Subtype: Link Rect: 59, 285, 97, 295 Annotation: Subtype: Link Rect: 497, 249, 535, 260 Annotation: Subtype: Link Rect: 213, 215, 250, 226 Annotation: Subtype: Link Rect: 256, 215, 292, 226 Annotation: Subtype: Link Rect: 95, 181, 132, 191 Annotation: Subtype: Link Rect: 139, 181, 175, 191 Annotation: Subtype: Link Rect: 404, 146, 442, 157 Annotation: Subtype: Link Rect: 173, 112, 211, 122 Annotation: Subtype: Link Rect: 321, 77, 359, 88 Page: Sequence: 36 Annotations: Annotation: Subtype: Link Rect: 131, 722, 169, 732 Annotation: Subtype: Link Rect: 419, 686, 457, 697 Annotation: Subtype: Link Rect: 363, 652, 400, 663 Annotation: Subtype: Link Rect: 384, 617, 422, 628 Annotation: Subtype: Link Rect: 267, 583, 305, 594 Annotation: Subtype: Link Rect: 336, 548, 373, 559 Annotation: Subtype: Link Rect: 380, 548, 416, 559 Annotation: Subtype: Link Rect: 255, 514, 293, 525 Annotation: Subtype: Link Rect: 299, 514, 335, 525 Annotation: Subtype: Link Rect: 503, 491, 541, 502 Annotation: Subtype: Link Rect: 207, 457, 244, 467 Annotation: Subtype: Link Rect: 339, 422, 376, 433 Annotation: Subtype: Link Rect: 501, 410, 560, 421 Annotation: Subtype: Link Rect: 56, 399, 560, 410 Annotation: Subtype: Link Rect: 56, 387, 177, 398 Annotation: Subtype: Link Rect: 350, 353, 388, 364 Annotation: Subtype: Link Rect: 82, 319, 119, 329 Annotation: Subtype: Link Rect: 188, 250, 226, 260 Annotation: Subtype: Link Rect: 377, 215, 414, 226 Annotation: Subtype: Link Rect: 410, 180, 448, 191 Annotation: Subtype: Link Rect: 454, 180, 490, 191 Annotation: Subtype: Link Rect: 291, 146, 328, 157 Annotation: Subtype: Link Rect: 334, 146, 370, 157 Annotation: Subtype: Link Rect: 292, 100, 329, 111 Annotation: Subtype: Link Rect: 335, 100, 371, 111 Annotation: Subtype: Link Rect: 136, 66, 173, 76 Annotation: Subtype: Link Rect: 179, 66, 216, 76 Page: Sequence: 37 Annotations: Annotation: Subtype: Link Rect: 171, 710, 209, 720 Annotation: Subtype: Link Rect: 140, 676, 178, 686 Annotation: Subtype: Link Rect: 405, 640, 443, 651 Annotation: Subtype: Link Rect: 167, 607, 204, 617 Annotation: Subtype: Link Rect: 375, 571, 413, 582 Annotation: Subtype: Link Rect: 176, 537, 214, 548 Annotation: Subtype: Link Rect: 259, 514, 297, 525 Annotation: Subtype: Link Rect: 303, 514, 339, 525 Annotation: Subtype: Link Rect: 519, 502, 557, 513 Annotation: Subtype: Link Rect: 59, 492, 95, 502 Annotation: Subtype: Link Rect: 330, 468, 368, 479 Annotation: Subtype: Link Rect: 374, 468, 410, 479 Annotation: Subtype: Link Rect: 167, 423, 204, 433 Annotation: Subtype: Link Rect: 333, 399, 371, 410 Annotation: Subtype: Link Rect: 419, 376, 456, 387 Annotation: Subtype: Link Rect: 104, 342, 142, 352 Annotation: Subtype: Link Rect: 342, 284, 380, 295 Annotation: Subtype: Link Rect: 59, 250, 97, 260 Annotation: Subtype: Link Rect: 103, 250, 139, 260 Annotation: Subtype: Link Rect: 59, 227, 97, 237 Annotation: Subtype: Link Rect: 103, 227, 139, 237 Annotation: Subtype: Link Rect: 222, 204, 260, 214 Annotation: Subtype: Link Rect: 266, 204, 302, 214 Annotation: Subtype: Link Rect: 250, 169, 288, 180 Annotation: Subtype: Link Rect: 59, 135, 97, 145 Annotation: Subtype: Link Rect: 113, 100, 150, 111 Annotation: Subtype: Link Rect: 494, 77, 531, 88 Page: Sequence: 38 Annotations: Annotation: Subtype: Link Rect: 353, 721, 391, 732 Annotation: Subtype: Link Rect: 104, 687, 142, 697 Annotation: Subtype: Link Rect: 122, 653, 160, 663 Annotation: Subtype: Link Rect: 59, 618, 97, 628 Annotation: Subtype: Link Rect: 103, 618, 139, 628 Annotation: Subtype: Link Rect: 262, 583, 299, 594 Annotation: Subtype: Link Rect: 306, 583, 342, 594 Annotation: Subtype: Link Rect: 519, 560, 557, 571 Annotation: Subtype: Link Rect: 59, 549, 95, 559 Annotation: Subtype: Link Rect: 191, 525, 228, 536 Annotation: Subtype: Link Rect: 207, 492, 244, 502 Annotation: Subtype: Link Rect: 264, 456, 302, 467 Annotation: Subtype: Link Rect: 297, 387, 335, 398 Annotation: Subtype: Link Rect: 59, 308, 97, 318 Annotation: Subtype: Link Rect: 91, 273, 128, 283 Annotation: Subtype: Link Rect: 152, 238, 190, 249 Annotation: Subtype: Link Rect: 338, 203, 376, 214 Annotation: Subtype: Link Rect: 272, 169, 310, 180 Annotation: Subtype: Link Rect: 316, 169, 352, 180 Annotation: Subtype: Link Rect: 231, 134, 269, 145 Annotation: Subtype: Link Rect: 178, 100, 216, 111 Page: Sequence: 39 Annotations: Annotation: Subtype: Link Rect: 59, 699, 97, 709 Annotation: Subtype: Link Rect: 383, 675, 421, 686 Annotation: Subtype: Link Rect: 520, 663, 557, 674 Annotation: Subtype: Link Rect: 423, 640, 461, 651 Annotation: Subtype: Link Rect: 127, 618, 164, 628 Annotation: Subtype: Link Rect: 95, 584, 133, 594 Annotation: Subtype: Link Rect: 95, 549, 133, 559 Annotation: Subtype: Link Rect: 145, 480, 182, 490 Annotation: Subtype: Link Rect: 373, 445, 410, 456 Annotation: Subtype: Link Rect: 395, 422, 433, 433 Annotation: Subtype: Link Rect: 439, 422, 475, 433 Annotation: Subtype: Link Rect: 517, 399, 554, 410 Annotation: Subtype: Link Rect: 442, 376, 479, 387 Annotation: Subtype: Link Rect: 59, 342, 97, 352 Annotation: Subtype: Link Rect: 333, 273, 371, 283 Annotation: Subtype: Link Rect: 354, 238, 391, 249 Annotation: Subtype: Link Rect: 371, 203, 408, 214 Annotation: Subtype: Link Rect: 363, 169, 400, 180 Annotation: Subtype: Link Rect: 381, 146, 419, 157 Annotation: Subtype: Link Rect: 196, 111, 233, 122 Annotation: Subtype: Link Rect: 150, 77, 188, 88 Annotation: Subtype: Link Rect: 443, 65, 480, 76 Page: Sequence: 40 Annotations: Annotation: Subtype: Link Rect: 519, 732, 557, 743 Annotation: Subtype: Link Rect: 162, 710, 199, 720 Annotation: Subtype: Link Rect: 145, 676, 182, 686 Annotation: Subtype: Link Rect: 158, 641, 195, 651 Annotation: Subtype: Link Rect: 367, 618, 405, 628 Annotation: Subtype: Link Rect: 411, 618, 447, 628 Annotation: Subtype: Link Rect: 249, 584, 286, 594 Annotation: Subtype: Link Rect: 78, 549, 116, 559 Annotation: Subtype: Link Rect: 250, 515, 288, 525 Annotation: Subtype: Link Rect: 258, 468, 295, 479 Annotation: Subtype: Link Rect: 412, 445, 450, 456 Annotation: Subtype: Link Rect: 510, 433, 548, 444 Annotation: Subtype: Link Rect: 95, 411, 133, 421 Annotation: Subtype: Link Rect: 163, 387, 200, 398 Annotation: Subtype: Link Rect: 197, 364, 235, 375 Annotation: Subtype: Link Rect: 228, 331, 266, 341 Annotation: Subtype: Link Rect: 272, 331, 308, 341 Annotation: Subtype: Link Rect: 104, 296, 142, 306 Annotation: Subtype: Link Rect: 148, 296, 184, 306 Annotation: Subtype: Link Rect: 519, 272, 557, 283 Annotation: Subtype: Link Rect: 59, 262, 95, 272 Annotation: Subtype: Link Rect: 487, 238, 524, 249 Annotation: Subtype: Link Rect: 465, 215, 503, 226 Annotation: Subtype: Link Rect: 471, 192, 508, 203 Annotation: Subtype: Link Rect: 152, 135, 189, 145 Annotation: Subtype: Link Rect: 405, 100, 442, 111 Annotation: Subtype: Link Rect: 446, 77, 484, 88 Page: Sequence: 41 Annotations: Annotation: Subtype: Link Rect: 118, 710, 155, 720 Annotation: Subtype: Link Rect: 161, 710, 197, 720 Annotation: Subtype: Link Rect: 513, 675, 551, 686 Annotation: Subtype: Link Rect: 463, 653, 501, 663 Annotation: Subtype: Link Rect: 237, 618, 275, 628 Annotation: Subtype: Link Rect: 499, 560, 537, 571 Annotation: Subtype: Link Rect: 213, 525, 251, 536 Annotation: Subtype: Link Rect: 350, 502, 388, 513 Annotation: Subtype: Link Rect: 405, 479, 443, 490 Annotation: Subtype: Link Rect: 422, 445, 459, 456 Annotation: Subtype: Link Rect: 159, 411, 196, 421 Annotation: Subtype: Link Rect: 59, 377, 97, 387 Annotation: Subtype: Link Rect: 103, 377, 139, 387 Annotation: Subtype: Link Rect: 59, 342, 97, 352 Annotation: Subtype: Link Rect: 103, 342, 139, 352 Annotation: Subtype: Link Rect: 106, 308, 143, 318 Annotation: Subtype: Link Rect: 150, 308, 186, 318 Annotation: Subtype: Link Rect: 275, 284, 311, 295 Annotation: Subtype: Link Rect: 245, 261, 282, 272 Annotation: Subtype: Link Rect: 289, 261, 325, 272 Annotation: Subtype: Link Rect: 503, 238, 540, 249 Annotation: Subtype: Link Rect: 145, 204, 182, 214 Annotation: Subtype: Link Rect: 113, 169, 151, 180 Annotation: Subtype: Link Rect: 237, 134, 275, 145 Annotation: Subtype: Link Rect: 519, 111, 557, 122 Annotation: Subtype: Link Rect: 59, 100, 95, 111 Annotation: Subtype: Link Rect: 494, 77, 532, 88 Page: Sequence: 42 Annotations: Annotation: Subtype: Link Rect: 242, 709, 280, 720 Annotation: Subtype: Link Rect: 450, 675, 488, 686 Annotation: Subtype: Link Rect: 275, 640, 312, 651 Annotation: Subtype: Link Rect: 488, 629, 525, 640 Annotation: Subtype: Link Rect: 59, 607, 97, 617 Annotation: Subtype: Link Rect: 234, 583, 272, 594 Annotation: Subtype: Link Rect: 374, 560, 412, 571 Annotation: Subtype: Link Rect: 445, 537, 482, 548 Annotation: Subtype: Link Rect: 154, 515, 192, 525 Annotation: Subtype: Link Rect: 198, 515, 234, 525 Annotation: Subtype: Link Rect: 165, 492, 203, 502 Annotation: Subtype: Link Rect: 209, 492, 245, 502 Annotation: Subtype: Link Rect: 205, 469, 242, 479 Annotation: Subtype: Link Rect: 249, 469, 285, 479 Annotation: Subtype: Link Rect: 481, 445, 519, 456 Annotation: Subtype: Link Rect: 122, 423, 159, 433 Annotation: Subtype: Link Rect: 59, 388, 97, 398 Annotation: Subtype: Link Rect: 184, 364, 222, 375 Annotation: Subtype: Link Rect: 497, 341, 534, 352 Annotation: Subtype: Link Rect: 468, 318, 506, 329 Annotation: Subtype: Link Rect: 397, 295, 435, 306 Annotation: Subtype: Link Rect: 227, 227, 264, 237 Annotation: Subtype: Link Rect: 190, 204, 227, 214 Annotation: Subtype: Link Rect: 234, 204, 270, 214 Annotation: Subtype: Link Rect: 500, 192, 537, 203 Annotation: Subtype: Link Rect: 104, 158, 142, 168 Annotation: Subtype: Link Rect: 158, 123, 195, 134 Annotation: Subtype: Link Rect: 408, 88, 445, 99 Page: Sequence: 43 Annotations: Annotation: Subtype: Link Rect: 400, 709, 437, 720 Annotation: Subtype: Link Rect: 230, 686, 268, 697 Annotation: Subtype: Link Rect: 95, 653, 133, 663 Annotation: Subtype: Link Rect: 140, 618, 178, 628 Annotation: Subtype: Link Rect: 184, 618, 220, 628 Annotation: Subtype: Link Rect: 441, 594, 478, 605 Annotation: Subtype: Link Rect: 485, 594, 521, 605 Annotation: Subtype: Link Rect: 193, 572, 230, 582 Annotation: Subtype: Link Rect: 236, 572, 272, 582 Annotation: Subtype: Link Rect: 109, 538, 146, 548 Annotation: Subtype: Link Rect: 153, 538, 189, 548 Annotation: Subtype: Link Rect: 399, 514, 437, 525 Annotation: Subtype: Link Rect: 443, 514, 479, 525 Annotation: Subtype: Link Rect: 520, 491, 557, 502 Annotation: Subtype: Link Rect: 419, 479, 456, 490 Annotation: Subtype: Link Rect: 519, 468, 556, 479 Annotation: Subtype: Link Rect: 220, 433, 257, 444 Annotation: Subtype: Link Rect: 308, 399, 346, 410 Annotation: Subtype: Link Rect: 216, 364, 253, 375 Annotation: Subtype: Link Rect: 260, 364, 296, 375 Annotation: Subtype: Link Rect: 519, 341, 557, 352 Annotation: Subtype: Link Rect: 59, 331, 95, 341 Annotation: Subtype: Link Rect: 186, 296, 223, 306 Annotation: Subtype: Link Rect: 229, 296, 265, 306 Annotation: Subtype: Link Rect: 59, 273, 97, 283 Annotation: Subtype: Link Rect: 103, 273, 139, 283 Annotation: Subtype: Link Rect: 338, 250, 375, 260 Checksum: d8861497 Type: CRC32 Checksum: b8ec673de60dec7161e9a4c15399afc9 Type: MD5 Checksum: b7cfe3970a040db891154390c33b2a4989f03a74 Type: SHA-1