<i>EGFR</i> exon 21 L858R as an acquired resistance mechanism to nivolumab in a lung cancer patient originally driver gene‐negative

Chen, Xia; Zeng, Fanxu; Zhang, Yongchang

doi:10.1111/1759-7714.13023

Cited by 6 publications

(4 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…56 Xia et al described an activating EGFR receptor mutation as an acquired resistance mechanism to the PD-1 antibody nivolumab in a lung cancer patient. 57 These data underline the rationale to combine immune checkpoint inhibitors with other targeted therapies such as bispecific T-cell engagers to evade resistance mechanisms and enhance the therapeutic efficacy.…”

Section: Discussionmentioning

confidence: 99%

Targeting the TIGIT-PVR immune checkpoint axis as novel therapeutic option in breast cancer

et al. 2019

View full text Add to dashboard Cite

Immune checkpoints are intensively investigated as targets in cancer therapy. T-cell immunoreceptor with immunoglobulin (Ig) and ITIM domains (TIGIT) and its ligand poliovirus receptor (PVR) are recently emerging as novel promising targets in immunotherapy. Here, we show that high expression of PVR represents an independent prognostic marker being associated with poor outcome for breast cancer patients. Furthermore, PVR mRNA, as well as protein expression, is associated with more aggressive breast cancer subtypes such as HER2 positive and triple-negative breast cancer. In vitro, blocking TIGIT or PVR resulted in enhanced immune cell-mediated lysis of breast cancer cell lines SKBR-3, MDA-MB-231, MDA-MB-468, and BT549 and additionally increased the cytotoxic effects of a bispecific T cell engager BiTE® antibody construct targeting EGFR. Taken together, our data identify the immune checkpoint factor PVR as a novel prognostic marker in breast cancer and indicate that blocking the TIGIT-PVR axis might represent a novel therapeutic option for the treatment of breast cancer patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Targeting the TIGIT-PVR immune checkpoint axis as novel therapeutic option in breast cancer

et al. 2019

View full text Add to dashboard Cite

show abstract

“…In the present study, we found that the PD-L1 and STAT3 inhibitors have an obvious therapeutic effect on LAD cell lines; and the EGFR mutation subtypes might influence the therapeutic efficacy. One case report has found that the L858R mutation is an acquired resistance mutation to nivolumab (PD-L1 inhibitor) [29], and patients with high PD-L1 expression may exhibit a poor response to EGFR-TKI. In addition, it has reported that the JAK/STAT3 pathway plays an important role in cancer proliferation and invasion, which could promote cancer aggression through inflammation or immunosuppression [30,31].…”

Section: Discussionmentioning

confidence: 99%

The mechanism of ABL1 upregulating the expression of PD-L1 and the therapeutic effect of PD-L1 and STAT3 inhibitors in lung adenocarcinoma

Tang¹,

Jiang²,

Li³

et al. 2021

neo

View full text Add to dashboard Cite

The upregulation of programmed cell death-ligand 1 (PD-L1) and continuous mutation of EGFR could induce chemoresistance in somatic cancers, however, the molecular mechanism of oncogene ABL1 in regulating the expression of PD-L1 in lung adenocarcinoma (LAD) remains unclear. In addition, the therapeutic effect of STAT3 and PD-L1 inhibitors in LAD is not fully understood. The ABL1 lentiviruses were used to transfect LAD cell lines (H1975, PC-9) with different EGFR mutation subtypes. Next, the expression of the JAK/STAT3 and PD-L1 pathway was detected followed by the treatment with STAT3 and PD-L1 inhibitors. Lastly, we observed the apoptosis and expression of STAT3 and PD-L1 before and after treatments in transfected and knocked down cell lines. The expression of ABL1 was upregulated by more than 3.71-fold and the expression of PD-L1 increased by 4.85-fold in lung cancer tissues compared with para-cancer tissues (both p<0.01), the ABL1 could induce upregulation of PD-L1 in LAD cell lines. Furthermore, the STAT3 inhibitor might induce more apoptosis than the PD-L1 inhibitor in both H1975 and PC-9 cell lines (both p<0.01) The STAT3 inhibitor combined with PD-L1 inhibitor had a synergistic effect on the PC-9 cell line, and the antagonistic effect was observed on the H1975 cell line. Furthermore, the expression of PD-L1 decreased almost equally after the PD-L1 inhibitor combined with a STAT3 inhibitor, or the STAT3 inhibitor alone (p>0.05). In addition, the STAT3 and PD-L1 decreased significantly after the STAT3 inhibitor compared with other treatments on the H1975 cell line (both p<0.01). To conclude, the EGFR mutation subtypes might influence the therapeutic efficacy in the treatment with PD-L1 inhibitor combined with STAT3 inhibitor on LAD cell lines.

show abstract

“…An autopsy of two immunotherapy failure patients also showed a sharply decrease of PD-L1 expression after immunotherapy ( 178 ). Acquired EGFR exon 21 L858R has been observed in a nivolumab resistant patient, which may also be a possible mechanism of secondary ICI resistance ( 179 ) ( Figure 2 ).…”

Section: Adverse Effects and Drug Resistance In Immunotherapymentioning

confidence: 99%

Cell adhesion molecules and immunotherapy in advanced non-small cell lung cancer: Current process and potential application

Yang

Miao²,

Yu³

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

Advanced non-small cell lung cancer (NSCLC) is a severe disease and still has high mortality rate after conventional treatment (e.g., surgical resection, chemotherapy, radiotherapy and targeted therapy). In NSCLC patients, cancer cells can induce immunosuppression, growth and metastasis by modulating cell adhesion molecules of both cancer cells and immune cells. Therefore, immunotherapy is increasingly concerned due to its promising anti-tumor effect and broader indication, which targets cell adhesion molecules to reverse the process. Among these therapies, immune checkpoint inhibitors (mainly anti-PD-(L)1 and anti-CTLA-4) are most successful and have been adapted as first or second line therapy in advanced NSCLC. However, drug resistance and immune-related adverse reactions restrict its further application. Further understanding of mechanism, adequate biomarkers and novel therapies are necessary to improve therapeutic effect and alleviate adverse effect.

show abstract

EGFR exon 21 L858R as an acquired resistance mechanism to nivolumab in a lung cancer patient originally driver gene‐negative

Cited by 6 publications

References 17 publications

Targeting the TIGIT-PVR immune checkpoint axis as novel therapeutic option in breast cancer

Targeting the TIGIT-PVR immune checkpoint axis as novel therapeutic option in breast cancer

The mechanism of ABL1 upregulating the expression of PD-L1 and the therapeutic effect of PD-L1 and STAT3 inhibitors in lung adenocarcinoma

Cell adhesion molecules and immunotherapy in advanced non-small cell lung cancer: Current process and potential application

Contact Info

Product

Resources

About