Different pathologic responses to neoadjuvant anti-PD-1 in primary squamous lung cancer and regional lymph nodes

Ling, Yun; Li, Ning; Li, Lin; Guo, Changyuan; Wei, Jiacong; Yuan, Ping; Tan, Fengwei; Tao, Xian; Wang, Shuhang; Wang, Zhijie; Wu, Ning; Wang, Jie; Jin, Ying; Gao, Shugeng

doi:10.1038/s41698-020-00135-2

Cited by 33 publications

(36 citation statements)

References 22 publications

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“…Tumors with no more than 10% viable tumor cells were considered to exhibit major pathological responses. The methods used to assess pathological response has been published previously 34 .…”

Section: Methodsmentioning

confidence: 99%

Genomic features and tumor immune microenvironment alteration in NSCLC treated with neoadjuvant PD-1 blockade

et al. 2022

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Several clinical trials have shown the safety and effectiveness of PD-1/PD-L1 inhibitors in neoadjuvant therapy in resectable non-small cell lung cancer (NSCLC). However, 18–83% patients can benefit from it. In this study, we aimed to assess the association of PD-L1 expression, tumor mutation burden, copy number alteration (CNA, including copy number gain and loss) burden with the pathologic response to neoadjuvant PD-1 blockade and investigate the changes in the tumor immune microenvironment (TIME) during neoadjuvant immunotherapy in NSCLC. Pre-immunotherapy treatment tumor samples from twenty-nine NSCLC patients who received neoadjuvant immunotherapy with sintilimab, an anti-PD-1 drug, were subjected to targeted DNA sequencing and PD-L1 immunochemistry staining. The pathological response was positively correlated with tumor proportion score (TPS) of PD-L1 and negatively correlated with copy number gain (CNgain) burden. Of note, the combination of CNgain burden and TPS can better stratify major pathological response (MPR) patients than did CNgain or TPS alone. Whereas, TMB showed a limited correlation with pathological regression. Additionally, PD-1 blockade led to an increase in CD8+PD-1−T cells which was clinically relevant to MPR as evaluated by multiplex immunofluorescence. A significant reduction in CD19+ cells was observed in the Non-MPR group but not in the MPR group, indicating the involvement of B cells in improving neoadjuvant immunotherapy response in NSCLC. Together, our study provides new data for the correlation of PD-L1 expression and genomic factors with drug response in neoadjuvant immunotherapy settings in NSCLC. The changes of TIME may provide novel insight into the immune responses to neoadjuvant anti-PD-1 therapy.

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Section: Methodsmentioning

confidence: 99%

Genomic features and tumor immune microenvironment alteration in NSCLC treated with neoadjuvant PD-1 blockade

et al. 2022

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“…These results suggest that the immune-response of IM in PT is similar to mLNs and stronger than of CT in PT, and IM region may serve as a frontline during the anti-tumor response, which results in immune-mediated features like the regression bed (27). According to the study of Ling et al, the PT and mLN show various immune phenotypes following neoadjuvant immune checkpoint inhibitor monotherapy (35). Considering that the pathological response of NSCLC after neoadjuvant immunochemotherapy is generally greater than that of anti-PD-1 monotherapy, the change of immune pattern by different neoadjuvant regimens remains to be investigated.…”

Section: Discussionmentioning

confidence: 84%

Different In Situ Immune Patterns Between Primary Tumor And Lymph Node In Non-Small Cell Lung Cancer: Potential Impact On Neoadjuvant Immunotherapy

Zhao

2021

Preprint

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Background Neoadjuvant immunotherapy is promising for locally-advanced non-small cell lung cancer (NSCLC). The in situ immune patterns, as predictor of PD-1/PD-L1 blockade outcomes, of the primary tumor (PT) and metastatic lymph nodes (mLNs) is unknown. Methods Multiplex immunofluorescence staining and multispectral imaging were used to evaluate the in situ immune patterns of T cells (CD3+) and cytotoxic T cells (CD8+) in terms of density, location (center of tumor [CT] and invasive margin [IM]), and the PD-L1 expression status of tumor cells and stromal T cells of paired PTs and mLNs in 38 stage-III NSCLCs.Results The densities of T cells and cytotoxic T cells were correlated between PTs and mLNs at both CT and IM. Higher densities of stromal T cells (S-CD3+) at CT and both S-CD3+ and cytotoxic T cells (S-CD8+) at IM were observed in mLNs compared to PTs, while in tumor compartment, there were no differences in the densities of T cells (T-CD3+) or cytotoxic T cells (T-CD8+). Only the density of stromal PD-L1-positive T cells (S-PD-L1+CD3+) at CT was correlated between PTs and mLNs, while the densities and frequencies of S-PD-L1+CD3+ at CT and IM of mLNs were higher than PTs. Combine positive score discordance of PD-L1 between PTs and mLNs was greater than tumor proportion score.Conclusions In situ immune patterns of T cells and cytotoxic T cells were different between PTs and mLNs in NSCLC. Higher densities of S-CD3+ and S-PD-L1+CD3+ in mLNs may result in better immune-mediated response to neoadjuvant immunotherapy.

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“…The pathologist experience might be crucial in defining 10% or less of viable cancer cells in the specimen (Tables 1 and 2). Tumor heterogeneity of the remaining tumor tissue may not reflect the efficacy of neoadjuvant treatment [28]. The important point is that none of the described studies are personalizing neoadjuvant therapy.…”

Section: Pathological Outcomesmentioning

confidence: 99%

Neoadjuvant and Adjuvant Immunotherapy in Non-Small Cell Lung Cancer—Clinical Trials Experience

Chmielewska

Stencel

Kalinka

et al. 2021

Cancers

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Across all tumor types, we observe that the role of immunotherapy has increased rapidly. Due to a number of potential advantages, it is considered in neoadjuvant treatment of localized tumors. In neoadjuvant settings, immunotherapy addresses micrometastatic diseases at the moment of their formation. However, some issues concerning neoadjuvant and adjuvant immunotherapy still has to be covered. The choice of drug and use of monotherapy or combination regimens remains unclear. The timing of surgery and preoperative evaluation of neoadjuvant immunotherapy efficacy is challenging. Although there is currently limited confirmed clinical data to support the use of immune checkpoint blockade in the neoadjuvant and adjuvant settings, there are many studies exploring this strategy in NSCLC patients.

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Different pathologic responses to neoadjuvant anti-PD-1 in primary squamous lung cancer and regional lymph nodes

Cited by 33 publications

References 22 publications

Genomic features and tumor immune microenvironment alteration in NSCLC treated with neoadjuvant PD-1 blockade

Genomic features and tumor immune microenvironment alteration in NSCLC treated with neoadjuvant PD-1 blockade

Different In Situ Immune Patterns Between Primary Tumor And Lymph Node In Non-Small Cell Lung Cancer: Potential Impact On Neoadjuvant Immunotherapy

Neoadjuvant and Adjuvant Immunotherapy in Non-Small Cell Lung Cancer—Clinical Trials Experience

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