Overcoming resistance to PD-1/PD-L1 inhibitors in esophageal cancer

Abstract

As the predominant treatment option of the immunotherapy for advanced esophageal cancer (EC), the application of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors brings new hope to clinical practice. However, a considerable portion of patients do not response to this therapy, meanwhile most patients sensitive to PD-1 or PD-L1 antibody initially will develop resistance to the treatment eventually. To break through the limits of clinical effect, it is of critical importance to make a profound understanding of the mechanisms of so called primary resistance and acquired resistance. Subsequently, exploring potent predictors to identify suitable patients for anti-PD-1/PD-L1 treatment and investigating efficient strategies to overcome drug resistance will be helpful to expend the benefit of immunotherapy. In the present view, we summarized the potential predictive factors for anti-PD-1/PD-L1 immunotherapy in EC, and demonstrated the plausible mechanisms of resistance to PD-1/PD-L1 blockade as well as its feasible solutions.

A new era in cancer treatment: harnessing ZIF-8 nanoparticles for PD-1 inhibitor delivery

“…By combining ZIF-8, a versatile nanoparticle for drug delivery, with PDL1 inhibitors, several benefits can be achieved. 7,48,70 Firstly, ZIF-8 can serve as a carrier for PDL1 inhibitors, protecting them from degradation and facilitating their targeted delivery to the tumor site. 48,70 This targeted delivery approach can enhance the accumulation of PDL1 inhibitors in the TME, maximizing their therapeutic effects while minimizing systemic toxicity.…”

“…7,48,70 Firstly, ZIF-8 can serve as a carrier for PDL1 inhibitors, protecting them from degradation and facilitating their targeted delivery to the tumor site. 48,70 This targeted delivery approach can enhance the accumulation of PDL1 inhibitors in the TME, maximizing their therapeutic effects while minimizing systemic toxicity. 7,70 Secondly, ZIF-8 can be functionalized to enhance the selectivity and specificity of PDL1 inhibition.…”

“…48,70 This targeted delivery approach can enhance the accumulation of PDL1 inhibitors in the TME, maximizing their therapeutic effects while minimizing systemic toxicity. 7,70 Secondly, ZIF-8 can be functionalized to enhance the selectivity and specificity of PDL1 inhibition. Surface modifications of ZIF-8 nanoparticles with targeting ligands or antibodies can facilitate the specific recognition and binding to cancer cells overexpressing PDL1.…”

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

“…For instance, EC patients with high PD-L1/PD-L2 expression, particularly patients in advanced stages, may have a poor prognosis[ 20 ]. Therefore, inhibiting PD-1/PD-L1 by blocking their interaction may restore the vigor and cytotoxicity of T cells in the TIME[ 18 ]. In recent years, immunotherapy involving checkpoint blockade targeting PD-1/PD-L1 has developed rapidly, becoming a first-line treatment for many cancers[ 17 , 48 ], but the efficacy of PD-1/PD-L1 blockade largely depends on the expression levels of PD-1/PD-L1 in the TME[ 19 , 49 , 50 ].…”

Breaking Barriers in Lung Cancer Research: The Intriguing Connection between IL-1β and PD-1/PD-L1 Pathways

“…Recent studies have shown that resistance to anti-PD therapy may be one of explanations for this widely varied response [4,54,55]. Primary and acquired resistance occur from immune-mediated mechanisms which derive from the TME and can occur at any step of the immunoregulatory process [4,54,56,57]. Primary resistance is the lack of initial response to ICIs, whereas acquired resistance is the lack of further response after initial improvement with ICIs [58].…”