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CCL21 Programs Immune Activity in Tumor Microenvironment

Sherven Sharma1,2,3, Pournima Kadam4, Steven Dubinett5,4,6

  • 1Department of Medicine, UCLA Lung Cancer Research Program, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. SSharma@mednet.ucla.edu.

Advances in Experimental Medicine and Biology
|February 16, 2020
PubMed

Insights

Chemokine CCL21 enhances anti-tumor immunity by organizing immune cells within the tumor microenvironment (TME). Delivering CCL21 may restore immune activity, improving cancer immunotherapy effectiveness when combined with immune evasion pathway inhibition.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • The tumor microenvironment (TME) often exhibits suppressed immune activity, hindering effective anti-cancer responses.
  • Immune escape mechanisms are prevalent in the TME, facilitating tumor evasion of the immune system.
  • Chemokine CCL21 plays a role in immune cell trafficking and organization.

Purpose of the Study:

  • To investigate the role of CCL21 in modulating the tumor microenvironment for enhanced anti-cancer immunity.
  • To explore strategies for delivering CCL21 to reactivate suppressed immune responses in cancer patients.
  • To evaluate the potential of combining CCL21 delivery with inhibition of immune evasion pathways for improved cancer immunotherapy.

Main Methods:

  • Analysis of CCL21's function in promoting dendritic cell (DC) and T cell colocalization within the TME.
  • Assessment of ectopic lymph node-like structures formation induced by CCL21.
  • Correlation of these structures with cancer patient prognosis.
  • Exploration of novel delivery strategies for CCL21 in preclinical models.
  • Investigation of combined therapeutic approaches involving CCL21 and immune evasion pathway inhibitors.

Main Results:

  • CCL21 promotes the formation of ectopic lymph node-like structures in the TME by organizing dendritic cells and T cells.
  • These CCL21-induced structures correlate with improved cancer prognosis.
  • Reactivation of downregulated immune activity in the TME is achievable through CCL21 delivery.
  • Combined inhibition of dominant immune evasion pathways alongside CCL21 administration shows promise.

Conclusions:

  • CCL21 is a key mediator in enhancing anti-tumor immune activity within the TME.
  • Targeted delivery of CCL21 represents a promising strategy to overcome immune suppression in cancer.
  • Combination therapy involving CCL21 and blockade of immune evasion pathways holds potential for developing effective cancer immunotherapies.
Keywords:
Activated T cellsAntigen-presenting cellsCCL21Dendritic cellsImmune activityImmune checkpoint blockadeImmune suppressionImmunotherapyProgrammed cell death protein 1 (PD-1)T cellsTumor microenvironment

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