Tumor and Tumor-Associated Macrophage Programmed Death-Ligand 1 Expression Is Associated With Adjuvant Chemotherapy Benefit in Lung Adenocarcinoma

Gross, David R.; Chintala, Navin K.; Vaghjiani, Raj G.; Grosser, Rachel; Tan, Kay See; Li, Xiaoyü; Choe, Jennie K.; Li, Yan; Emoto, Katsura; Zheng, Hua; Dux, Joseph; Cheema, Waseem; Bott, Matthew; Travis, William D.; Isbell, James M.; Li, Bob T.; Jones, David R.; Adusumilli, Prasad S.

doi:10.1016/j.jtho.2021.09.009

Cited by 23 publications

(22 citation statements)

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“…To survive under immune pressure, LUAD develops a few mechanisms to evade immune surveillance, primarily via expressing immune checkpoints. For instance, PD-L1 expression on tumor-associated macrophages or tumor cells correlates to prolonged survival with adjuvant chemotherapy ( 32 ). Here, immune checkpoints ADORA2A, BTLA, CD4, and TIM3 displayed higher levels in C2, with lower levels of LAG3, PD-L1, and IDO1 in C1.…”

Section: Discussionmentioning

confidence: 99%

“…The National Comprehensive Cancer Network guidelines have recommended testing specific molecular as well as immune markers in patients with advanced/metastatic LUAD, thus evaluating applicability for targeted therapy or immunotherapy ( 36 ). Stage II to III LUAD patients receive adjuvant chemotherapy to target the premetastatic niche that persists following curative resection ( 32 ). Here, the C1 subtype more possibly responded to JNK inhibitor VIII, BI-D1870, RO-3306, A-443654, VX-680, SL-0101-1, S -trityl- l -cysteine, BI-2536, mitomycin C, CCT018159, KU-55933, and docetaxel.…”

Section: Discussionmentioning

confidence: 99%

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Immune infiltration landscape on prognosis and therapeutic response and relevant epigenetic and transcriptomic mechanisms in lung adenocarcinoma

et al. 2022

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ObjectiveLung adenocarcinoma (LUAD) is the most prevalent lung cancer subtype, but its immune infiltration features are not comprehensively understood. To address the issue, the present study was initiated to describe the immune infiltrations across LUAD from cellular compositional, functional, and mechanism perspectives.MethodsWe adopted five LUAD datasets (GSE32863, GSE43458, GSE75037, TCGA-LUAD, and GSE72094). Differentially expressed genes between LUAD and controls were selected for co-expression network analysis. Risky immune cell types were determined for classifying LUAD patients as diverse subtypes, followed by a comparison of antitumor immunity and therapeutic response between subtypes. Then, LUAD- and subtype-related key module genes affected by DNA methylation were determined for quantifying a scoring scheme. EXO1 was chosen for functional analysis via in vitro assays.ResultsTwo immune cell infiltration-based subtypes (C1 and C2) were established across LUAD, with poorer prognostic outcomes and lower infiltration of immune cell types in C1. Additionally, C1 presented higher responses to immune checkpoint blockade and targeted agents (JNK inhibitor VIII, BI-D1870, RO-3306, etc.). The scoring system (comprising GAPDH, EXO1, FYN, CFTR, and KLF4) possessed higher accuracy in estimating patients’ prognostic outcomes. EXO1 upregulation contributed to the growth, migration, and invasion of LUAD cells. In addition, EXO1 facilitated PD-L1 and sPD-L1 expression in LUAD cells.ConclusionAltogether, our findings offer a comprehensive understanding of the immune infiltration landscape on prognosis and therapeutic response of LUAD as well as unveil potential epigenetic and transcriptomic mechanisms, which might assist personalized treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immune infiltration landscape on prognosis and therapeutic response and relevant epigenetic and transcriptomic mechanisms in lung adenocarcinoma

et al. 2022

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“…Several studies have examined the relationship between PD-L1 expression and the benefit of postoperative adjuvant chemotherapy. A recent study suggested that PD-L1 expression in tumor cells is associated with improved survival with adjuvant chemotherapy (HR, 3.02; 95%CI, 1.69–5.40) [ 57 ]. In contrast, the LACE-Bio study showed that neither tumor nor immune cell PD-L1 expression is predictive of clinical benefits from adjuvant chemotherapy [ 58 ].…”

Section: Current Biomarker Candidates For Perioperative Patients With...mentioning

confidence: 99%

Benefits from Adjuvant Chemotherapy in Patients with Resected Non-Small Cell Lung Cancer: Possibility of Stratification by Gene Amplification of ACTN4 According to Evaluation of Metastatic Ability

Tozuka

Noro

Seike

et al. 2022

Cancers

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Surgical treatment is the best curative treatment option for patients with non-small cell lung cancer (NSCLC), but some patients have recurrence beyond the surgical margin even after receiving curative surgery. Therefore, therapies with anti-cancer agents also play an important role perioperatively. In this paper, we review the current status of adjuvant chemotherapy in NSCLC and describe promising perioperative therapies, including molecularly targeted therapies and immune checkpoint inhibitors. Previously reported biomarkers of adjuvant chemotherapy for NSCLC are discussed along with their limitations. Adjuvant chemotherapy after resective surgery was most effective in patients with metastatic lesions located just outside the surgical margin; in addition, these metastatic lesions were the most sensitive to adjuvant chemotherapy. Thus, the first step in predicting patients who have sensitivity to adjuvant therapies is to perform a qualified evaluation of metastatic ability using markers such as actinin-4 (ACTN4). In this review, we discuss the potential use of biomarkers in patient stratification for effective adjuvant chemotherapy and, in particular, the use of ACTN4 as a possible biomarker for NSCLC.

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“… 4 10 14 Some of these were recently explored in the context of early-stage lung cancers relative to PD-L1 co-expression for predictivity of adjuvant chemotherapy benefit. 15 …”

Section: Introductionmentioning

confidence: 99%

Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer

Henick

Villarroel‐Espíndola

Datar

et al. 2022

J Immunother Cancer

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BackgroundDespite the prominent role of innate immunity in the antitumor response, little is known about the myeloid composition of human non-small cell lung cancer (NSCLC) with respect to histology and molecular subtype. We used multiplexed quantitative immunofluorescence (QIF) to measure the distribution and clinical significance of major myeloid cell subsets in large retrospective NSCLC collections.MethodsWe established a QIF panel to map major myeloid cell subsets in fixed human NSCLC including 4’,6-Diamidino-2-Phenylindole for all cells, pancytokeratin for tumor-epithelial cells, CD68 for M1-like macrophages; and CD11b plus HLA-DR to interrogate mature and immature myeloid cell populations such as myeloid derived suppressor cells (MDSCs). We interrogated 793 NSCLCs represented in four tissue microarray-based cohorts: #1 (Yale, n=379) and #2 (Greece, n=230) with diverse NSCLC subtypes; #3 (Yale, n=138) with molecularly annotated lung adenocarcinomas (ADC); and #4 (Yale, n=46) with patient-matched NSCLC and morphologically-normal lung tissue. We examined associations between marker levels, myeloid cell profiles, clinicopathologic/molecular variables and survival.ResultsThe levels of CD68+ M1 like macrophages were significantly lower and the fraction of CD11b+/HLA-DR− MDSC-like cells was prominently higher in tumor than in matched non-tumor lung tissues. HLA-DR was consistently higher in myeloid cells from tumors with elevated CD68 expression. Stromal CD11b was significantly higher in squamous cell carcinomas (SCC) than in ADC across the cohorts and EGFR-mutated lung ADCs displayed lower CD11b levels than KRAS-mutant tumors. Increased stromal CD68- and HLA-DR-expressing cells was associated with better survival in ADCs from two independent NSCLC cohorts. In SCC, increased stromal CD11b or HLA-DR expression was associated with a trend towards shorter 5-year survival.ConclusionsNSCLCs display an unfavorable myeloid immune contexture relative to non-tumor lung and exhibit distinct myeloid-cell profiles across histologies and presence of major oncogenic driver-mutations. Elevated M1-like stromal proinflammatory myeloid cells are prognostic in lung ADC, but not in SCC.

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Tumor and Tumor-Associated Macrophage Programmed Death-Ligand 1 Expression Is Associated With Adjuvant Chemotherapy Benefit in Lung Adenocarcinoma

Cited by 23 publications

References 50 publications

Immune infiltration landscape on prognosis and therapeutic response and relevant epigenetic and transcriptomic mechanisms in lung adenocarcinoma

Immune infiltration landscape on prognosis and therapeutic response and relevant epigenetic and transcriptomic mechanisms in lung adenocarcinoma

Benefits from Adjuvant Chemotherapy in Patients with Resected Non-Small Cell Lung Cancer: Possibility of Stratification by Gene Amplification of ACTN4 According to Evaluation of Metastatic Ability

Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer

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