Abstract
The article "Enhancing CAR-T Efficacy: The Role of Anti PD-1/PD-L1 Checkpoint Inhibitors
in Modern Cancer Treatment" provides an exhaustive study on CAR-T cell therapy and
its role in cancer treatment, focusing on the problem of T-cell exhaustion and tumor
immune evasion. Anti-PD-1/PD-L1 checkpoint inhibitors are said to help achieve enhanced
CAR-T therapy by countering immune suppression within the tumor microenvironment.
The introduction emphasizes the success level of CAR-T cells, especially in B-cell
hematologic malignancies, while humbly candid in its limitation concerning solid tumors
through mechanisms of immunosuppression. Of specific interest herein are the PD-1
and PD-L1 pathways as key immune checkpoints exploited by cancer to escape an immune
response. To elaborate on this, it also explains how tumors upregulate PD-L1 to prevent
T-cell functions through T-cell exhaustion, which entails depression in cytokine production
and proliferation. The article explains the mechanisms of T-cell exhaustion: chronic
antigen exposure, transcriptional reprogramming, metabolic dysfunction, and the suppressive
nature of the tumor microenvironment. All these mechanisms combined lead to a loss
of T-cell efficacy in counteracting tumor progression. The PD-1/PD-L1 axis preserves
T-cell exhaustion and inhibits a strong immune response against the tumor. The paper
puts forth the argument that the combination of CAR-T cell therapy with PD-1/PD-L1
checkpoint inhibitors leads to the reversal of immune suppression, improving T-cell
function and persistence. A review of the preclinical and clinical trials, especially
for solid tumor malignancies, puts forth advantages as well as challenges. Such challenges
are experienced in terms of T-cell exhaustion, immunosuppressive tumor microenvironments,
optimization of a dose, issues of toxicity, and inconsistent clinical outcomes.
Keywords
Cancer immunotherapy - PD-1/PD-L1 - T cell exhaustion - conventional chemotherapy
Bibliographical Record
Rishi Kant, Prashanjit Roy, Amandeep Kaur, Ranjeet Kumar. Enhancing CAR-T Efficacy:
The Role of Anti PD-1/PD-L1 Checkpoint Inhibitors in Modern Cancer Treatment. Journal
of Coloproctology 2025; 45: s00451809675.
DOI: 10.1055/s-0045-1809675
