The soldiers needed to be awakened: Tumor-infiltrating immune cells

Wang, Yaping; Wang, Zhe; Zhuling, Chu; Ruolei, Li; Fan, Pengyu; Guo, Lili; Cheng, Jin; Zhang, Bo; Liuyin, Liu; Hou, Guoqing; Wang, Yaolin; Hou, Niuniu; Ling, Rui

doi:10.3389/fgene.2022.988703

Cited by 6 publications

(3 citation statements)

References 478 publications

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“…Different kinds of immune cells have different functions in tumor development. Tregs, 37 Myeloid‐derived suppressor cells (MDSCs), 38 cancer‐associated fibroblasts (CAFs) 39 and M2 macrophages 40 are generally regarded as tumor accelerative cells, while M1 macrophages, NK cells 41 and CD8 + T cells are recognized as antitumor cells. By analyzing three independent ccRCC sequencing data (TCGA‐KIRC, ICGC‐RECA, and ICI‐RCC) using two different algorithms, we find that LY96 is always positively associated with M2 macrophages, which is considered important for generation of inhibitory ccRCC TME 42 .…”

Section: Discussionmentioning

confidence: 99%

Gene LY96 is an M2 macrophage‐related biomarker and is associated with immunosuppression in renal cell carcinoma

Li,

Meng,

et al. 2023

MedComm – Oncology

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Lymphocyte Antigen 96 (LY96) was identified as an oncogene in several tumors. However, its role in renal cancer has not been explored. In the study, LY96 is identified abnormally expressed using several public kidney cancer sequencing data. The expression level of LY96 is validated using paired clinical samples. Survival analyses and ROC curves are used to examine its prognostic and diagnostic value. Gene sets enrichment analyses (GSEA) show LY96 might influence immune processes. Then immune infiltration analyses results suggest that LY96 is positively correlated with M2 macrophages infiltration in RCC. Single‐cell data are used to verify its association with macrophages. Moreover, LY96 is positively with various immune scores and might affect the efficacy of immunotherapy. Drug screening results show LY96 might be the target of vemurafenib and etoposide. Further experiments confirm the spatial co‐localization of LY96 and M2, and knocking down LY96 can inhibit M2 polarization. Cell viability experiments indicate that knocking down LY96 would result in a decrease in the resistance of M2 macrophages to etoposide. The study shows LY96 could act as an unfavorable biomarker for RCC and possibly contribute to cancer progression by promoting the infiltration of M2 macrophage. LY96 could be a novel therapeutic target for RCC.

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Section: Discussionmentioning

confidence: 99%

Gene LY96 is an M2 macrophage‐related biomarker and is associated with immunosuppression in renal cell carcinoma

Li,

Meng,

et al. 2023

MedComm – Oncology

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“… 7 Similarly, Shimura et al found a correlation between low LMR and MDSC, with the low LMR group having a higher proportion of MDSC than the high LMR group. 26 While MDSC can be divided into mononuclear-MDSC and polymorphic MDSC, mononuclear-MDSC can differentiate into TAM, and polymorphic-MDSC can produce reactive oxygen species, inhibit T-cell function, 27 promote T regulatory cell formation, 28 and promote tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Combined LMR and CEA Dynamic Monitoring in Postoperative Colorectal Cancer Patients

Chen,

Zhang,

Qian

et al. 2023

JIR

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Purpose We aim to investigate the clinical significance of dynamic changes in the lymphocyte-to-monocyte ratio (LMR) and neutrophil-lymphocyte ratio (NLR) in peripheral blood at different time points combined with CEA in the prediction of postoperative-recurrence-in-patients with colorectal cancer (CRC). Patients and Methods This study collected 357 patients with stage I–III CRC between 2016 and April 2018. The dynamic changes from preoperative to postoperative LMR (p-LMR-p) and NLR (p-NLR-p) were analyzed using COX regression for multivariate analysis. Logistic regression was used to investigate whether the dynamic changes from post-treatment to pre-end of follow-up LMR (p-LMR-f) and NLR (p-NLR-f) were independent risk factors for CRC recurrence and to construct a predictive model. Internal validation using bootstrapping was performed to validate the discrimination ability of the model. The models’ discriminative effect, calibration degree, and clinical utility were assessed. Results In both the total cohort and the adjuvant therapy group, the dynamic changes of p-LMR-p (High-High vs Low-Low: p=0.006; HR:2.210, 95% CI: 1.256–3.890) were found to be independent prognostic factors for recurrence-free survival (RFS) in CRC patients. Additionally, logistic regression analysis revealed that N stage, CEA, LMR of pre-end of follow-up (f-LMR), and p-LMR-f were independent risk factors for CRC recurrence. In the total cohort, the p-LMR-f had an area under the curve (AUC) of 0.704, with a sensitivity of 64% and a specificity of 75.3%. By combining p-LMR-f with CEA, a predictive model was constructed, which showed an AUC of 0.913 (0.986–0.913) in the total cohort and an AUC of 0.924 (0.902–0.924) in the adjuvant therapy group during internal validation using bootstrapping. Conclusion Dynamic changes in LMR can be used to predict the prognosis of CRC and serve as a biomarker for predicting CRC recurrence. Combined with CEA, it can improve the predictive performance for detecting CRC recurrence.

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“…The presence and density of tumor-associated macrophages are correlated with poor prognosis and resistance to GC treatment [ 10 ]. Antigen-specific cytotoxic CD8 + T cells directly kill tumor cells or mediate their apoptosis through the Fas/FasL signaling pathway [ 11 ]. After the initial antigen stimulation is removed, the memory cells shrink and are found in the tissue and lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

Histological Type, Cytotoxic T Cells and Macrophages in the Tumor Microenvironment Affect the PD-L1 Status of Gastric Cancer

et al. 2023

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Gastric cancer (GC) therapies include gastrectomy and chemoradiotherapy. The tumor immune microenvironment (TME) has implications for potential immunotherapy. We analyzed the expression of PD-L1, CD8, CTLA-4 and IFN-γ in the tumor and regional lymph node (LN) of patients with GC and compared it with clinical and pathological data. Paraffin blocks were collected from 97 patients undergoing gastrectomy/lymphadenectomy for GC. Double immunohistochemistry was performed for CD8 and PD-L1 and double immunofluorescence for CTLA-4 and IFN-γ. Statistical significance was set at p < 0.05. PD-L1 expression in tumor cells was associated with intestinal GC type (p = 0.046), the density of macrophages and CD8 + T cells (p < 0.001, both). The median number of CD8+ T cells was higher in PD-L1-positive than in -negative tumors. A cut-off of 28.5 CD8 + T cells in one high-magnification field predicted PD-L1-positive tumors (AUROC 0.797, sensitivity 74.2%, specificity 77.3%). IFN-γ expression in tumor cells was found in 37 GCs and was positively associated with CTLA4+ lymphocytes in the LN (p = 0.027) and CTLA4+/IFN-γ+ in tumors and the LN (all p < 0.001). The median overall survival (OS) was 17 months. In the group of deceased patients, IFN-γ expression in metastases correlated with lower OS (RHO = −0.314, p = 0.008). PD-L1 expression in tumor cells correlated with CD8 + T cells and macrophages in the TME and IFN-γ expression with suppressive CTLA4+/IFNγ+ immune cells in the TME and LN.

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The soldiers needed to be awakened: Tumor-infiltrating immune cells

Cited by 6 publications

References 478 publications

Gene LY96 is an M2 macrophage‐related biomarker and is associated with immunosuppression in renal cell carcinoma

Gene LY96 is an M2 macrophage‐related biomarker and is associated with immunosuppression in renal cell carcinoma

Prognostic Value of Combined LMR and CEA Dynamic Monitoring in Postoperative Colorectal Cancer Patients

Histological Type, Cytotoxic T Cells and Macrophages in the Tumor Microenvironment Affect the PD-L1 Status of Gastric Cancer

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