Periodically Pulsed Immunotherapy in a Mathematical Model of Tumor, CD4<sup>+</sup> T Cells, and Antitumor Cytokine Interactions

<div>(a) The bifurcation diagram for <span class="nowrap"><svg height="12.7178pt" id="M365" style="vertical-align:-3.42947pt" version="1.1" viewbox="-0.0498162 -9.28833 38.1062 12.7178" width="38.1062pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M558 587C558 666 497 712 432 712C379 712 330 691 284 650C212 586 178 508 148 348L71 -65C49 -185 35 -229 23 -235L27 -261C49 -259 101 -251 124 -224C131 -216 138 -178 159 -24C171 66 197 200 227 356C264 550 295 668 393 668C443 668 479 632 479 575C479 516 446 458 383 418C361 404 344 398 318 397L296 350C395 338 460 281 460 192C460 110 411 40 300 40C258 40 215 55 192 69L181 51C191 18 222 -16 266 -16C308 -16 351 1 397 26C471 67 545 142 545 221C545 315 486 365 401 395C469 437 558 498 558 587Z" id="g113-224"></path></g><g transform="matrix(.013,0,0,-0.013,11.186,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z" id="g117-34"></path></g><g transform="matrix(.013,0,0,-0.013,22.449,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path></g><g transform="matrix(.013,0,0,-0.013,28.689,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z" id="g113-47"></path></g><g transform="matrix(.013,0,0,-0.013,31.653,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z" id="g113-50"></path></g></svg>.</span> (b) The detailed development of the fold-homoclinic bifurcation. (c) The change of dynamics at <span class="nowrap"><svg height="12.584pt" id="M366" style="vertical-align:-3.29567pt" version="1.1" viewbox="-0.0498162 -9.28833 57.2701 12.584" width="57.2701pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M530 686C535 705 530 712 521 712C504 712 448 684 359 674L358 648H393C437 648 439 646 429 593L400 435C372 447 345 448 332 448C286 448 194 414 144 373C68 311 23 203 23 111C23 26 57 -12 91 -12C120 -12 147 3 188 29C227 54 290 102 341 170H343L322 71C308 6 320 -12 341 -12C373 -12 442 27 501 96L485 120C455 91 422 67 408 67C401 67 401 76 404 91C440 294 479 473 530 686ZM387 375L355 241C326 187 200 53 142 53C126 53 109 73 109 130C109 217 154 337 218 381C240 396 265 404 297 404S372 390 387 375Z" id="g113-101"></path></g><g transform="matrix(.0091,0,0,-0.0091,7.15,3.132)"><path d="M618 181C565 77 513 26 413 26C264 26 151 150 151 336C151 486 240 625 407 625C516 625 573 582 600 475L634 483C627 540 622 581 613 638C585 643 518 665 435 665C211 665 46 526 46 315C46 158 157 -15 406 -15C480 -15 564 4 594 12C612 43 638 121 651 168L618 181Z" id="g58-65"></path></g><g transform="matrix(.0091,0,0,-0.0091,13.274,3.132)"><path d="M43 650V617C122 612 130 606 130 522V128C130 44 122 37 34 32V0H275C400 0 497 25 573 82C652 142 698 229 698 350C698 445 662 518 613 565C549 625 456 650 327 650H43ZM217 544C217 580 220 591 229 599C240 607 264 613 311 613C380 613 437 599 482 570C561 523 598 436 598 336C598 177 511 40 324 40C248 40 217 61 217 135V544Z" id="g58-66"></path></g><g transform="matrix(.0091,0,0,-0.0091,20.045,3.132)"><path d="M462 177V227H365V632H320C217 496 116 350 21 208V177H284V109C284 43 280 38 190 31V0H451V31C369 38 365 43 365 108V177H462ZM284 227H88C155 336 218 430 282 519H284V227Z" id="g50-53"></path></g><g transform="matrix(.0065,0,0,-0.0065,24.476,-.065)"><path d="M578 242V297H351V519H286V297H59V242H286V-6H351V242H578Z" id="g180-36"></path></g><g transform="matrix(.013,0,0,-0.013,33.325,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z" id="g117-34"></path></g><g transform="matrix(.013,0,0,-0.013,44.588,0)"><path d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z" id="g113-51"></path></g><g transform="matrix(.013,0,0,-0.013,50.828,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path></g></svg>.</span></div>

Computational and Mathematical Methods in Medicine

fig10

Figure 10

Figure 10: Periodically Pulsed Immunotherapy in a Mathematical Model of Tumor, CD4<sup>+</sup> T Cells, and Antitumor Cytokine Interactions 

Computational and Mathematical Methods in Medicine

Periodically Pulsed Immunotherapy in a Mathematical Model of Tumor, CD4+ T Cells, and Antitumor Cytokine Interactions

Figure 10

Periodically Pulsed Immunotherapy in a Mathematical Model of Tumor, CD4⁺ T Cells, and Antitumor Cytokine Interactions