Recent advances in immunotherapy for non-small-cell lung cancer

Suzuki, Hiroyuki; Owada, Yohei; Watanabe, Yuzuru; Inoue, Takuya; Fukuharav, Mitsuro; Yamaura, Takumi; Mutoh, Satoshi; Okabe, Naoyuki; Yaginuma, Hiroshi; Hasegawa, T.; Yasuda, Atsushi; Ohsugi, Jun; Hoshino, Mika; Higuchi, Mitsunori; Shio, Yutaka; Gotoh, Mitsukazu

doi:10.4161/hv.26919

Cited by 16 publications

(7 citation statements)

References 46 publications

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“…Previous studies have suggested that optimal activation of effector T cells required 2 signals: an antigen-specific signal generated by the interaction between the antigen and the TCR (MHC-Ag-TCR) and a second signal resulting from the interaction between costimulatory molecules (B7-CD27). 25,26 We showed in this study that EGFR mutations caused a weakening of the immunogenicity, which impaired the antigen specific signal and caused the T cells to become blind to the tumor cells. As we all know, the CheckMate 026 clinical trial comparing first-line nivolumab with standard chemotherapy in NSCLC patients with PD-L1 5% was failed.…”

Section: Discussionmentioning

confidence: 84%

EGFR mutation correlates with uninflamed phenotype and weak immunogenicity, causing impaired response to PD-1 blockade in non-small cell lung cancer

et al. 2017

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Patients with mutations showed unfavorable response to programmed cell death-1 (PD-1) blockade immunotherapy in non-small cell lung cancer (NSCLC). Yet the underlying association between mutation and immune resistance remains largely unclear. We performed an integrated analysis of PD-ligand 1(PD-L1)/CD8 expression and mutation profile based on the repository database and resected early-stage NSCLC in Guangdong Lung Cancer Institute (GLCI). Meanwhile, 2 pool-analyses were set to clarify the correlation between mutation and PD-L1 expression, and the association of status with response to anti-PD-1/L1 therapy. Pool-analysis of 15 public studies suggested that patients with mutations had decreased PD-L1 expression (odds ratio: 1.79, 95% CI: 1.10-2.93; P = 0.02). Analysis of The Cancer Genome Atlas (TCGA) and the GCLI cohort confirmed the inverse correlation between mutation and PD-L1 expression. Furthermore, patients with mutation showed a lack of T-cell infiltration and shrinking proportion of PD-L1/CD8 TIL (P = 0.034). Importantly, patients with mutations, especially the sensitive subtype, showed a significantly decreased mutation burden, based on analysis of the discovery and validation sets. Finally, a pool-analysis of 4 randomized control trials confirmed that patients with mutation did not benefit from PD-1/L1 inhibitors (Hazard ratio [HR] = 1.09, P = 0.51) while patients with wild-type did (HR = 0.73, P< 0.00001). This study provided evidence of a correlation between mutations and an uninflamed tumor microenvironment with immunological tolerance and weak immunogenicity, which caused an inferior response to PD-1 blockade in NSCLCs.

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Section: Discussionmentioning

confidence: 84%

EGFR mutation correlates with uninflamed phenotype and weak immunogenicity, causing impaired response to PD-1 blockade in non-small cell lung cancer

et al. 2017

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“…Recently, aberrant PD-L1 and PD-L2 expression by cancer cells has been reported in many human malignancies (17)(18)(19). A series of clinical trials concerning the systemic administration of therapeutic antibodies for blocking PD-1 or PD-L1 have shown a promising clinical effect in various tumors (20,21).…”

Section: Introductionmentioning

confidence: 99%

Relationship between expression of PD-L1 and PD-L2 on esophageal squamous cell carcinoma and the antitumor effects of CD8+ T cells

Leng

Qin

et al. 2015

Oncology Reports

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Abstract. The programmed death-1 (PD-1)/programmed death-ligands (PD-Ls) signal pathway has been implicated as a potential immune escape mechanism in several human cancers. However, the studies of PD-1/PD-Ls pathway in esophageal squamous cell carcinoma (ECSS) are not yet sufficient. The current study investigated the expression of PD-L1, PD-L2 and PD-1 in ESCC tissues. The correlations between the expression of these proteins and clinical histopathological parameters were analyzed. Then the stable transfected Ec109 cell lines overexpressing PD-L1/PD-L2 were established by plasmid transfection successfully. Ec109 and CD8 + T cells were co-cultured to analyze the effects of PD-1/PD-Ls signal pathway on the function of CD8 + T cells including proliferation, apoptosis and interferon-γ production. We found that PD-L1-positive patients had significantly poorer prognosis than the negative patients, while their prognosis was not related to PD-L2 expression. The count of PD-1 + TILs (tumor-infiltrating lymphocytes) was negatively correlated with both PD-L1 and PD-L2 expression. In functional studies, we found that PD-1/PD-Ls signal pathway was able to downregulate the function of CD8 + T lymphocyte and its function could be restored by blocking the signal pathway. This indicates that PD-1/PD-Ls may prevent effective antitumor immunity, which provides important evidence to delineate the cellular immune deficiency mechanism in ESCC. Therefore, PD-1/PD-Ls are predicted to become novel targets for ESCC immunotherapy.

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“…Novel immunotherapy strategy is pending on histological definition of targets in tumor, and those targets can change in time [ 36 , 37 ]. So it is essential to search, for example, PD-L1 positivity for confirming reactivity of lung cancer on nivolumab before initiating treatment [ 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

Role of Rebiopsy in Relapsed Non-Small Cell Lung Cancer for Directing Oncology Treatments

Jekunen¹

2015

Journal of Oncology

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Background. Currently, few rebiopsies are performed in relapses of advanced non-small cell lung cancer. They are not customary in clinical practice of lung cancer. However, it is not possible to properly target treatments in cases of relapse without knowing the nature of new lesions. Design. This paper comprehensively summarizes the available literature about rebiopsy and broadly discusses the importance of rebiopsy in advanced non-small cell lung cancer. Results. Altogether 560 abstracts were used as material for further analysis. 19 articles were about clinical rebiopsy in lung cancer and were reviewed in detailed manner. Conclusions. This review shows that rebiopsy is feasible in non-small cell lung cancer, and success rates can be high if rebiopsy is accompanied by adequate evaluation before biopsy. Its use may resolve the difficulties in sampling bias and detecting changes in cancer characteristics. In cases where treatment was selected based on tissue characteristics that then change, the treatment selection process must be repeated while considering new characteristics of the tumor. Rebiopsy may be used to predict therapeutic resistance and consequently redirect targeted therapies. Such knowledge may resolve the difficulties in sampling bias and also in selecting preexisting clones or formulating drug-resistant ones. Rebiopsy should be performed more often in non-small cell lung cancer.

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Recent advances in immunotherapy for non-small-cell lung cancer

Abstract: However, although therapeutic cancer vaccines are generally thought to be safe, severe adverse events should be monitored carefully when using immune checkpoint inhibitors. Here, we discuss recent advances and future perspectives of immunotherapy for patients with NSCLC.

Cited by 16 publications

References 46 publications

EGFR mutation correlates with uninflamed phenotype and weak immunogenicity, causing impaired response to PD-1 blockade in non-small cell lung cancer

EGFR mutation correlates with uninflamed phenotype and weak immunogenicity, causing impaired response to PD-1 blockade in non-small cell lung cancer

Relationship between expression of PD-L1 and PD-L2 on esophageal squamous cell carcinoma and the antitumor effects of CD8+ T cells

Role of Rebiopsy in Relapsed Non-Small Cell Lung Cancer for Directing Oncology Treatments

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