TIGIT Blockade Exerts Synergistic Effects on Microwave Ablation Against Cancer

Chen, Yaping; Huang, Hao; Li, Yuan; Xiao, Wenlu; Liu, Yingting; Chen, Rongzhang; Zhu, Yongwei; Zheng, Xiao; Wu, Changping; Chen, Lüjun

doi:10.3389/fimmu.2022.832230

Cited by 18 publications

(33 citation statements)

References 61 publications

(71 reference statements)

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“…For example, it has been suggested that in the tumor model established by 4T1 breast cancer cells, the MWA can activate the T-cell immune response, and the combination therapy based on MWA can significantly induce the Th1-type anti-tumor response [10]. Moreover, we have previously confirmed that MWA combined with TIGIT blockade exerts synergistic effects against cancer in contrast to MWA or TIGIT blockade alone [12].…”

Section: Introductionsupporting

confidence: 68%

“…The MC38 cells (mouse colon cancer cell line) in the present study have been used in our previous report [12]. MC38 cells were maintained in DMEM supplemented with 10% (v/v) fetal bovine serum (FBS, Gibco, Thermo Fisher Scientific, USA), 100 U/mL penicillin, and 100 µg/ mL streptomycin.…”

Section: Cell Line and Micementioning

confidence: 99%

“…Despite its late stage in clinical trials, the role of LAG3 in the immune cellular network has not yet been fully addressed. Our previous studies have shown that radiofrequency ablation (RFA) combined with PD-1 blockade, or MWA combined with TIGIT blockade, can serve as important combinational therapeutic strategies [9,12]. Moreover, we have also analyzed publicly available single-cell RNA-sequencing (scRNA-seq) data from the pancreatic ductal adenocarcinoma (PDAC) mouse model with and without RFA therapy, and found that LAG3 expression is up-regulated in CD8 + T and CD4 + T cell subsets after RFA, suggesting the potential possibilities for the design of combination therapeutic strategy [20].…”

Section: Introductionmentioning

confidence: 99%

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LAG3 blockade coordinates with microwave ablation to promote CD8+ T cell-mediated anti-tumor immunity

et al. 2022

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Background The immune checkpoint inhibitors (ICIs) combined with other therapeutic strategies have shown exciting results in various malignancies, and ICIs have now become the gold standard for current cancer treatment. In several preclinical and clinical investigations, ablation coupled with immunotherapy has proved to be quite effective. Our previous studies have shown that ablation coupled with ICI is a potential anti-cancer regimen for colorectal cancer liver metastases (CRLM). Furthermore, we have reported that following microwave ablation (MWA), the expression of LAG3 is up-regulated in tumor microenvironment (TME), indicating that LAG3 is implicated in the regulation of immunosuppressive immune response, and combination therapy of MWA and LAG3 blockade can serve as a promising therapeutic strategy against cancer. Methods The expression of LAG3 was investigated in this study utilizing a preclinical mouse model treated with MWA. Moreover, we monitored the tumor development and survival in mice to assess the anti-cancer effects of MWA alone or in combination with LAG3 blockade. Flow cytometry was also used to phenotype the tumor-infiltrating lymphocytes (TILs) and CD8+ T cell effector molecules. We finally analyzed the single-cell RNA sequencing (scRNA-seq) data of infiltrating CD45+ immune cells in the tumors from the MWA alone and MWA combined with LAG3 blockade groups. Results After MWA, the expression of LAG3 was up-regulated on sub-populations of TILs, and introducing LAG3 blockade to MWA postponed tumor development and extended survival in the MC38 tumor model. Flow cytometry and scRNA-seq revealed that LAG3 blockade in combination with MWA markedly boosted the proliferation and the function of CD8+ TILs, leading to altered myeloid cells in the TME. Conclusion Combination therapy of LAG3 blockade and MWA was a unique therapeutic regimen for some solid tumors, and such combination therapy might reprogram the TME to an anti-tumor manner.

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Section: Introductionsupporting

confidence: 68%

Section: Cell Line and Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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LAG3 blockade coordinates with microwave ablation to promote CD8+ T cell-mediated anti-tumor immunity

et al. 2022

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“…TA is considered a safe treatment for primary lung cancer ( 7 , 20 , 21 ). As an alternative therapy to surgical resection, TA causes irreversible damage to tumor cells using thermal energy ( 14 , 31 , 32 ). While previous studies have shown that TA is beneficial for stage I NSCLC patients ( 7 , 18 , 33 ), however, there is minimal data on the use of TA in stage II-III NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

Survival benefit of thermal ablation therapy for patients with stage II-III non-small cell lung cancer: A propensity-matched analysis

Yang

et al. 2022

Front. Oncol.

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BackgroundThermal ablation (TA) is considered a safe alternative to surgical resection for the treatment of non-small cell lung cancer (NSCLC). While previous studies have shown that TA is beneficial for stage I NSCLC patients, however, few have reported on TA efficacy in patients with stage II-III NSCLC. The current study investigated the impact of TA on the overall survival (OS) and cancer-specific survival (CSS) of patients with stage II-III NSCLC.MethodsData on patients with stage II-III NSCLC who did not undergo surgical resection between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM), Kaplan-Meier survival curves, and Cox regression were used for statistical analyses.ResultsA total of 57,959 stage II-III NSCLC patients who did not undergo surgical resection were included in this study, 261 of whom received TA. Overall, TA was associated with a longer OS (p = 0.035) and CSS (p = 0.005) than non-ablation. After 1:3 PSM, 252 patients receiving TA and 732 patients not receiving ablation were enrolled in the matched cohort. The OS (p = 0.047) and CSS (p = 0.029) remained higher in the TA group than in the non-ablation group after PSM. Cox regression analysis showed that age, sex, primary tumor site, pathological type, tumor size, radiotherapy, chemotherapy, and thermal ablation were independently associated with OS and CSS (p <0.05). Subgroup analysis found that the advantages of TA were more pronounced among individuals ≥70 years of age, with tumor size ≤3.0 cm, or who did not receive radiotherapy.ConclusionTA could be an effective alternative treatment for stage II-III NSCLC patients unsuitable for surgical resection, particularly those ≥70 years of age, with tumor size ≤3.0 cm, or who have not received radiotherapy.

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“…Single-cell RNA-seq (scRNA-seq) data analysis and different expression gene analysis Our scRNA-seq data were processed by the methods as we previously described. 41 Briefly, cells with less than 6000 unique molecular identifiers (UMIs) count, 10% mitochondrial gene count, and 40% ribosomal gene count were used for integration of multiple scRNA-seq, dimension reduction and unsupervised clustering. All visualization plots were applied by Seurat function and ggplot2 package.…”

Section: Tcr Repertoire Analysismentioning

confidence: 99%

IL1R2 increases regulatory T cell population in the tumor microenvironment by enhancing MHC-II expression on cancer-associated fibroblasts

Chen

Huang

Zheng

et al. 2022

J Immunother Cancer

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BackgroundRegulatory T cells (Treg) are an integral part of the tumor immune tolerance. Carcinoma-associated fibroblasts (CAFs) is a pivotal driver for accumulation of Treg cells in the tumor microenvironment (TME). The molecular nature underpinning Treg cells and CAFs coupling needs to be further defined.MethodsThe Il1r2flox/floxFoxp3Cre mice were generated to establish the conditional knock-out of Il1r2 in Foxp3+ Tregs in vivo. Using the MC38 tumor model, we evaluated the antitumor efficacy of immune checkpoint inhibitors (ICIs) and further analyzed the immune profiling of the TME by multicolor flow cytometry. Single-cell RNA sequencing of the whole tumor tissues, TCR repertoire analysis of sorted CD3+ TILs were also performed.ResultsWe showed that IL1 receptor 2 (IL1R2), a decoy receptor that neutralizes IL1, was highly expressed in Treg cells in the TME. In addition, we found that Il1r1 was largely expressed in the CAFs, suggesting IL1R2 plays a role in modulating crosstalk between Tregs and CAFs. We further demonstrated that Il1r2 deficiency in Treg cells led to greater antitumor efficacy of ICI, decreased Tregs and increased CD8+ T cells in the TME, as well as reduced levels of T cell dysfunction. Mechanistically, we showed that IL1 inhibited major histocompatibility complex class II (MHC-II) expression on fibroblasts and Treg-specific Il1r2 deletion led to a decrease in genes associated with MHC-II antigen presentation in CAFs.ConclusionsOur study established a critical role of IL1 signaling in inhibiting Treg-mediated tumor immune suppression through downregulating MHC-II antigen presentation in CAFs.

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TIGIT Blockade Exerts Synergistic Effects on Microwave Ablation Against Cancer

Cited by 18 publications

References 61 publications

LAG3 blockade coordinates with microwave ablation to promote CD8+ T cell-mediated anti-tumor immunity

LAG3 blockade coordinates with microwave ablation to promote CD8+ T cell-mediated anti-tumor immunity

Survival benefit of thermal ablation therapy for patients with stage II-III non-small cell lung cancer: A propensity-matched analysis

IL1R2 increases regulatory T cell population in the tumor microenvironment by enhancing MHC-II expression on cancer-associated fibroblasts

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