CD95L and Anti-Tumor Immune Response: Current Understanding and New Evidence

Area of Science:

• Immunology
• Cell Biology
• Oncology

Background:

• Fas Ligand (FasL)/CD95 Ligand (CD95L) induces apoptosis in physiological immune regulation.
• Non-apoptotic CD95 activation in cancer promotes invasiveness, progression, and stemness.
• The CD95/CD95L pathway has complex roles in tumor biology and the immune response.

Purpose of the Study:

• To review the evolving understanding of CD95/CD95L signaling in cancer.
• To emphasize the non-apoptotic activities of CD95/CD95L on tumor cells, microenvironment, and immune cells.
• To present evidence for CD95/CD95L's role in anti-tumor immunity and therapeutic interventions.

Main Methods:

• Literature review and synthesis of current research on CD95/CD95L signaling in malignancies.
• Analysis of the impact of CD95/CD95L on tumor cell function, tumor microenvironment, and immune cells.
• Examination of therapeutic strategies involving selective CD95L inhibition.

Main Results:

• CD95/CD95L signaling exhibits dual roles: apoptosis induction and promotion of cancer progression.
• Non-apoptotic CD95 activation is implicated in enhanced cancer cell invasiveness and stemness.
• Evidence supports CD95/CD95L signaling's involvement in anti-tumor immune responses across various cancers.

Conclusions:

• The CD95/CD95L pathway is a critical regulator in cancer, with both pro- and anti-tumorigenic functions.
• Targeting CD95L, particularly through selective inhibition, offers potential therapeutic avenues.
• Combination therapies involving CD95L inhibition with RT, chemotherapy, or ICIs show promise for cancer treatment.