Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a membrane glycoprotein expressed by activated effector T cells (Teffs) and participates in the repression of T cell proliferation, cell cycle progression, and cytokine production. Currently, antibodies targeting CTLA-4, ipilimumab and tremelimumab are widely used as a therapeutic approach in a variety of human malignancies. However, their detailed mechanism remains unclear. CTLA-4 blockade is used as a therapeutic approach for the treatment of cancer through competing with CD28-positive co-stimulation for binding to their shared B7 ligands or exhibiting a direct inhibitory effect on signaling molecules in the cytoplasmic tail. At present, antibodies for targeting CTLA-4 or in combination with other therapies significantly reinforced the anti-tumor effect and improved the prognosis of malignant disease. In addition, severe adverse events of targeting CTLA-4 therapy could be a challenge for the development of this therapeutic strategy.
CTLA-4 targeting faces two related challenges: suboptimal efficacy and increased toxicity. Although treatments targeting CTLA-4 have produced promising activities against malignant diseases, the drug-induced adverse events, termed “immune-related adverse events, (irAEs)” have been observed in some patients due to non-tumor-specific T cells activated by CTLA-4 blockade. The observations of anti-CTLA-4 versus anti-PD in humans differ sharply from those in preclinical models where anti-PD reagents are typically less effective than anti-CTLA-4 antibodies in cancer immunotherapy. While it is possible that preclinical models did not reflect human diseases, it is of interest to ask whether the low efficacy and high toxicity of CTLA-4 in humans is due to either the inherent limit of the CTLA-4 target or because of a fundamental knowledge gap on how to target CTLA-4.
This Research Topic will give a comprehensive overview of the anti-CTLA-4 cancer immunotherapy that critically affects tumor immunity, with particular emphasis on more effective and safe ways to preserve this novel immune checkpoint in the scope of cancer immunotherapy. We welcome the submission of Original Papers, Reviews, Mini-reviews, and Perspective articles. The themes addressed by this Research Topic will include, but are not limited to, the following:
• Tregs and CTLA-4 in cancer.
• More effective ways to apply anti-CTLA-4 antibody to other tumors than melanoma.
• The combination of anti-CTLA-4 antibodies with other immune checkpoint antibodies in a neoadjuvant therapy setting.
• Ways to tackle the low efficacy and high toxicity of anti-CTLA-4 antibody therapy.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a membrane glycoprotein expressed by activated effector T cells (Teffs) and participates in the repression of T cell proliferation, cell cycle progression, and cytokine production. Currently, antibodies targeting CTLA-4, ipilimumab and tremelimumab are widely used as a therapeutic approach in a variety of human malignancies. However, their detailed mechanism remains unclear. CTLA-4 blockade is used as a therapeutic approach for the treatment of cancer through competing with CD28-positive co-stimulation for binding to their shared B7 ligands or exhibiting a direct inhibitory effect on signaling molecules in the cytoplasmic tail. At present, antibodies for targeting CTLA-4 or in combination with other therapies significantly reinforced the anti-tumor effect and improved the prognosis of malignant disease. In addition, severe adverse events of targeting CTLA-4 therapy could be a challenge for the development of this therapeutic strategy.
CTLA-4 targeting faces two related challenges: suboptimal efficacy and increased toxicity. Although treatments targeting CTLA-4 have produced promising activities against malignant diseases, the drug-induced adverse events, termed “immune-related adverse events, (irAEs)” have been observed in some patients due to non-tumor-specific T cells activated by CTLA-4 blockade. The observations of anti-CTLA-4 versus anti-PD in humans differ sharply from those in preclinical models where anti-PD reagents are typically less effective than anti-CTLA-4 antibodies in cancer immunotherapy. While it is possible that preclinical models did not reflect human diseases, it is of interest to ask whether the low efficacy and high toxicity of CTLA-4 in humans is due to either the inherent limit of the CTLA-4 target or because of a fundamental knowledge gap on how to target CTLA-4.
This Research Topic will give a comprehensive overview of the anti-CTLA-4 cancer immunotherapy that critically affects tumor immunity, with particular emphasis on more effective and safe ways to preserve this novel immune checkpoint in the scope of cancer immunotherapy. We welcome the submission of Original Papers, Reviews, Mini-reviews, and Perspective articles. The themes addressed by this Research Topic will include, but are not limited to, the following:
• Tregs and CTLA-4 in cancer.
• More effective ways to apply anti-CTLA-4 antibody to other tumors than melanoma.
• The combination of anti-CTLA-4 antibodies with other immune checkpoint antibodies in a neoadjuvant therapy setting.
• Ways to tackle the low efficacy and high toxicity of anti-CTLA-4 antibody therapy.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.