HLA class II molecule HLA-DRA identifies immuno-hot tumors and predicts the therapeutic response to anti-PD-1 immunotherapy in NSCLC

Mei, Jie; Jiang, Guanyu; Chen, Yundi; Xu, Yongrui; Wan, Yuan; Chen, Ruo; Liu, Feng; Mao, Wenjun; Zheng, Mingfeng; Xu, Junying

doi:10.1186/s12885-022-09840-6

Cited by 14 publications

(12 citation statements)

References 55 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The activation status of TME infiltrates has been reported to influence the presence and functionality of tumor-reactive T cells [43][44][45][46] , a feature that was also reported for NSCLC 42,47 . PD-L1, which is expressed on activated immune cells, plays a key role in suppressing inflammatory immune responses 48 .…”

Section: Presence and Activation Status Of Neutrophils Negatively Cor...mentioning

confidence: 74%

Tertiary lymphoid structure-related immune infiltrates in NSCLC tumor lesions correlate with low tumor-reactivity of TIL products

Castenmiller,

Kanagasabesan,

Guislain

et al. 2024

Preprint

View full text Add to dashboard Cite

Adoptive transfer of tumor infiltrating lymphocytes (TIL therapy) has shown great potential for the treatment of solid cancers, including non-small cell lung cancer (NSCLC). However, not all patients benefit from this therapy, and the parameters that define the likelihood of TIL products to be tumor reactive are to date unknown. Defining prognostic markers that correlate with high level of tumor-reactivity is key for achieving better tailored immunotherapies.To determine whether the composition of immune cell infiltrates correlates with the tumor-reactivity of expanded TIL products, we employed multi-parameter flow cytometry to characterize the immune cell infiltrates from 26 early-stage, and 20 late-stage NSCLC tumor lesions. Unbiased flow cytometry analysis with Cytotree and Spearman’s Rank Correlation was used to correlate immune infiltrates with the expansion rate, immune cell activation and T cell differentiation state, and the anti-tumor response of TIL products generated from the same lesions.The composition of tumor immune infiltrates was highly variable between patients, irrespective of the disease stage. High percentages of B cell infiltrates positively correlated with the presence of conventional CD4+T cells, and an overall increase of naïve T cell infiltrates. In contrast, high B cell infiltrates negatively correlated with the tumor-reactivity of expanded TIL products, as defined by cytokine production upon exposure to autologous tumor digest. Tumors with high B cell infiltrates contained IgD+BCL6+B cells and CXCR5+BLC6+CD4+T cell infiltrates and an increased percentage of naïve CD8+T cells, indicative of the presence of tertiary lymphoid structures (TLS) in tumors with high B cell infiltrates.This study reveals that the composition of immune cell infiltrates in NSCLC tumors associates with the functionality of expanded TIL products from NSCLC tumor lesions. Importantly, the tumor-responsiveness of TIL products negatively correlated with the presence of TLS-associated immune infiltrates in tumors. Our finding may thus help improve patient selection for TIL therapy.

show abstract

Section: Presence and Activation Status Of Neutrophils Negatively Cor...mentioning

confidence: 74%

Tertiary lymphoid structure-related immune infiltrates in NSCLC tumor lesions correlate with low tumor-reactivity of TIL products

Castenmiller,

Kanagasabesan,

Guislain

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown that reduced HLA-DRA correlated with a lower immune enrichment score of CD4 + T cells 43 and could predict the response to anti-programmed death-1 immunotherapy in NSCLC. 44 Furthermore, we examined the association of these prognostic genes with the drug sensitivity profiles of NSCLC chemotherapeutic drugs in 135 NSCLC cell lines. We found that prognostic genes showed significant differential expression in mRNA and protein level in sensitive vs. resistant NSCLC cell lines (2-sample t-tests; p < 0.05).…”

Section: Resultsmentioning

confidence: 99%

The dynamic dysregulated network identifies stage-specific markers during lung adenocarcinoma malignant progression and metastasis

Wang¹,

Liu²,

Liu³

et al. 2022

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

“…Based on the abundance of tumor-infiltrating lymphocytes (TILs), TME can be classified into hot tumors (inflamed type) and cold tumors (desert and excluded type) [ 24 ]. Hot tumors generally exhibit richer immune infiltrations and better immunotherapy response than cold tumors [ 25 , 26 , 27 ], while poor TILs infiltrations are associated with immunotherapy resistance [ 28 , 29 ]. Thus, accurately distinguishing cold tumors from hot tumors can improve immunotherapy efficiency and reduce unnecessary medical costs.…”

Section: Discussionmentioning

confidence: 99%

Cuproptosis Depicts Immunophenotype and Predicts Immunotherapy Response in Lung Adenocarcinoma

Zhou

Cheng

et al. 2023

JPM

View full text Add to dashboard Cite

Background: Although significant progress has been made in immunotherapy for lung adenocarcinoma (LUAD), there is an urgent need to identify effective indicators to screen patients who are suitable for immunotherapy. Systematically investigating the cuproptosis-related genes (CRGs) in LUAD may provide new ideas for patients’ immunotherapy stratification. Method: We comprehensively analyzed the landscape of 12 CRGs in a merged TCGA and GEO LUAD cohort. We investigated the associations between tumor microenvironment and immunophenotypes. We utilized a risk score to predict the prognosis and immunotherapy response for an individual patient. Additionally, we conducted CCK-8 experiments to evaluate the impact of DLGAP5 knockdown on A549 cell proliferation. Result: We utilized an integrative approach to analyze 12 CRGs and differentially expressed genes (DEGs) in LUAD samples, resulting in the identification of two distinct CRG clusters and two gene clusters. Based on these clusters, we generated immunophenotypes and observed that the inflamed phenotype had the most abundant immune infiltrations, while the desert phenotype showed the poorest immune infiltrations. We then developed a risk score model for individual patient prognosis and immunotherapy response prediction. Patients in the low-risk group had higher immune scores and ESTIMATE scores, indicating an active immune state with richer immune cell infiltrations and higher expression of immune checkpoint genes. Moreover, the low-risk group exhibited better immunotherapy response according to IPS, TIDE scores, and Imvigor210 cohort validation results. In addition, our in vitro wet experiments demonstrated that DLGAP5 knockdown could suppress the cell proliferation of A549. Conclusion: Novel cuproptosis molecular patterns reflected the distinct immunophenotypes in LUAD patients. The risk model might pave the way to stratify patients suitable for immunotherapy and predict immunotherapy response.

show abstract

HLA class II molecule HLA-DRA identifies immuno-hot tumors and predicts the therapeutic response to anti-PD-1 immunotherapy in NSCLC

Cited by 14 publications

References 55 publications

Tertiary lymphoid structure-related immune infiltrates in NSCLC tumor lesions correlate with low tumor-reactivity of TIL products

Tertiary lymphoid structure-related immune infiltrates in NSCLC tumor lesions correlate with low tumor-reactivity of TIL products

The dynamic dysregulated network identifies stage-specific markers during lung adenocarcinoma malignant progression and metastasis

Cuproptosis Depicts Immunophenotype and Predicts Immunotherapy Response in Lung Adenocarcinoma

Contact Info

Product

Resources

About