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Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Immunodeficiency Diseases

Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
There are three main causes of immunodeficiency disorders...

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Stem-cell Based Engineered Immunity Against HIV Infection in the Humanized Mouse Model
11:38

Stem-cell Based Engineered Immunity Against HIV Infection in the Humanized Mouse Model

Published on: July 2, 2016

Modeling interleukin-2-based immunotherapy in AIDS pathogenesis.

Marcel Joly1, Darci Odloak

  • 1Process Control and Simulation Laboratory, University of São Paulo, Av. Prof. Luciano Gualberto, Trav. 3, São Paulo SP 05508-900, Brazil. joly@petrobras.com.br

Journal of Theoretical Biology
|June 29, 2013
PubMed
Summary
This summary is machine-generated.

Interleukin-2 (IL-2) therapy expands CD4(+) T-cells in HIV infection. This expansion is primarily due to IL-2 modulating cell death pathways, not increased cell survival.

Keywords:
AICDAIDSAPCCCFCNSDAEENVEnv-CD4 cross-linking mediated apoptosisFDCHAARTHEVHIVIFN-γIL-12IL-2IUIVSTImmune systemImmunotherapyInternational UnitLTMHCMIUPBPCDPCRPSVET-lymphocyteTATTat-induced apoptosisVTCacquired immunodeficiency syndromeactivation-induced cell deathantigen presenting cellscell–cell fusioncentral nervous system compartmentdifferential-algebraic equationsfollicular dendritic cellshigh endothelial venuleshighly active antiretroviral therapyhuman immunodeficiency virusinterferon γinterleukin-12interleukin-2intracellular viral stock transferencelymphoid tissue compartmentmajor histocompatibility complexmillion International Unitspassive cell deathperipheral blood compartmentpolarized secretion of viral envelopespolymerase chain reactionvirus-to-cell

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Area of Science:

  • Immunology
  • Virology
  • Mathematical Biology

Background:

  • HIV infection critically depletes CD4(+) T-cells, impacting immune function.
  • Interleukin-2 (IL-2) is a cytokine known to promote T-cell proliferation.
  • Previous research suggested increased CD4(+) T-cell survival as the mechanism for IL-2 therapy benefits in HIV.

Purpose of the Study:

  • To investigate the dynamics of CD4(+) T-cell responses to IL-2 therapy in HIV-infected individuals.
  • To elucidate the precise mechanisms driving CD4(+) T-cell expansion under IL-2 treatment.

Main Methods:

  • Analysis of CD4(+) T-cell dynamics during continuous and intermittent intravenous IL-2 administration.
  • Application of multivariate regression models and comprehensive mathematical modeling.
  • Investigation into the role of IL-2 in modulating apoptotic pathways.

Main Results:

  • IL-2 administration leads to expressive, selective, and sustained CD4(+) T-cell expansions.
  • The primary mechanism is not increased CD4(+) T-cell survival, contrary to prior conclusions.
  • IL-2 modulates Fas-dependent apoptotic pathways, including activation-induced cell death (AICD) and viral protein-triggered apoptosis.

Conclusions:

  • IL-2 therapy's benefit in expanding CD4(+) T-cells in HIV is linked to reduced apoptosis.
  • Modulation of apoptotic pathways by IL-2 is the key driver of T-cell expansion.
  • Findings challenge previous assumptions about IL-2's mechanism of action in HIV.