Lung cancer remains one of the most prevalent and deadly malignancies worldwide, with persistently low five-year survival rates. This poor prognosis is primarily attributed to challenges such as difficulties in early diagnosis, high tumor heterogeneity, and strong therapeutic resistance. Although recent advances in targeted therapies and immune checkpoint inhibitors have significantly improved the prognosis of some patients, the majority still encounter primary or secondary resistance. Galectin-3, a multifunctional glycan-binding protein, is constitutively expressed in pulmonary tissues. Its expression encompasses bronchial and alveolar epithelial cells, the pulmonary vasculature, and resident immune cells. Galectin-3 plays a central role in lung cancer progression by regulating tumor cell proliferation, immune evasion, and angiogenesis. The complex immunosuppressive mechanisms within the tumor microenvironment not only facilitate tumor growth and metastasis but also partially limit the efficacy of cancer immunotherapies. Overcoming these barriers requires the exploration of novel regulatory targets to break through therapeutic bottlenecks. This review systematically elucidates the mechanisms by which galectin-3 interacts with immune cells (e.g., T cells, macrophages) in the tumor microenvironment and evaluates its potential as a therapeutic target, including inhibitor development and combination immunotherapy strategies. The findings aim to provide a theoretical foundation for advancing galectin-3 as a novel therapeutic target in lung cancer and offer new perspectives for overcoming current immunotherapy resistance.
.
Humans ; Lung Neoplasms/pathology* ; Tumor Microenvironment/immunology* ; Galectin 3/genetics* ; Animals ; Immunomodulation ; Immunotherapy

Brain metastasis was a common metastasis site and leading cause of death in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors had improved survival of NSCLC patients with positive drive gene. It also brings good news to NSCLC patients with positive drive gene and brain metastases. However, there is still no effective treatment for NSCLC patients with drive gene-negative and brain metastases. In recent years, immunotherapy has made breakthrough progress and become important first and second line treatment options of NSCLC especially in patients with drive gene-negative. The role of immunotherapy in specific populations of NSCLC-brain metastasis patients, especially drive gene-negative patients has become the focus of attention. In this report, we review the research progress of immunotherapy in NSCLC with brain metastases, especially in driver-negative patients, analyze the limitations of existing research and future challenge.
.
Brain Neoplasms ; immunology ; secondary ; therapy ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; Humans ; Immunotherapy ; methods ; Lung Neoplasms ; genetics ; pathology ; Patient Selection

BACKGROUND: Previous studies have shown that the neutrophil-to-lymphocyte ratio (NLR) has a significant impact on the prognosis of many malignant tumors such as gastric cancer, colorectal cancer and pancreatic cancer, but the study on the prognosis of patients with resectable lung adenocarcinoma is less. The aim of this study is to investigate the correlation between the NLR and the clinicopathologic features of adenocarcinoma of lung patients who underwent radical pneumonectomy. Furthermore, this study aimed to clarify the predictive and prognostic significance of NLR in patients who underwent pneumonectomy for lung adenocarcinoma. METHODS: This study reviewed the medical records of 163 patients with lung adenocarcinoma who underwent pneumonectomy. The receiver operating characteristic (ROC) curve and Youden index were used to determine the cut-off value of the NLR. Survival curves were described by Kaplan-Meier method and compared by Log-rank test. The univariate and multivariate analyses were performed with the Cox proportional hazard model to identify the prognostic factors. RESULTS: When the NLR value was 2.96, the Youden index was maximal, with a sensitivity of 77.5% and a specificity of 75.9%. The 5-year survival rate in the low NLR group was higher than that in the high NLR group (P<0.05). The univariate and multivariate analyses showed that TNM staging and NLR were independent factors in predicting survival rate. CONCLUSIONS The NLR value was a simple and useful tool to predict the prognosis of lung adenocarcinoma after radical pneumonectomy.
Adenocarcinoma ; diagnosis ; immunology ; pathology ; surgery ; Adenocarcinoma of Lung ; Aged ; Cell Count ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms ; diagnosis ; immunology ; pathology ; surgery ; Lymphocytes ; cytology ; Male ; Middle Aged ; Neoplasm Staging ; Neutrophils ; cytology ; Pneumonectomy ; Prognosis ; ROC Curve ; Retrospective Studies

Paragonimiasis has been continuously decreasing in Korea. However, it still occurs by ingesting raw or incompletely cooked fresh water crab or crayfish. The diagnosis of paragonimiasis is challenging because of its rarity. It may be confused with other inflammatory disease or carcinomatosis. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has lower risk of complications such as bleeding, perforation than percutaneous fine needle aspiration. EUS-FNA is more accurate and popular method to find mucosal or submucosal tumors and the lesions of several organs. Benign and malignant tumors, infectious diseases have been diagnosed by EUS-FNA, but there was no report describing the use of EUS-FNA for diagnosing paragonimiasis. Herein, we present a 47-year-old male patient with paragonimiasis diagnosed by EUS-FNA. Imaging studies revealed mass lesions in the lung and peritoneal cavity, which was eventually confirmed as paragonimiasis using EUS-FNA.
Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Enzyme-Linked Immunosorbent Assay ; Humans ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Paragonimiasis/*diagnosis/diagnostic imaging/immunology ; Positron-Emission Tomography ; Tomography, X-Ray Computed

OBJECTIVETo explore the effects of radiofrequency ablation(RFA) on immune system and lung metastasis in a mouse model of triple negative breast cancer 4T1.

METHODSMouse breast cancer 4T1 cells were injected into the right hind limb of female Bal B/c mice. When the tumor size was 6-8 mm in diameter, RFA was used to treat the transplanted breast cancer in mice. We examined the splenic lymphocyte subsets by flow cytometry at different time points after RFA. Fourteen days after treatment, we sacrificed the mice of both control and treatment groups, counted the number of lung metastatic nodules, and detected the changes of splenic lymphocyte subsets by flow cytometry.

RESULTSRFA basically eliminated the orthotopic carcinoma with a low local recurrence rate. After the RFA treatment, the amount of spleic CD4⁺ T cells, CD8⁺ T cells, B cells, NK and NKT cells was increased. Fourteen days after the RFA treatment, all mice were sacrificed, and the lung metastatic nodules were 24 ± 18 in the control group and 81 ± 35 in the RFA-treated group (P = 0.012). The mechanism of suppression of metastatic lung cancers was related to the increase of splenic CD4⁺ T cells, CD8⁺ T cells, B cells and NK cells, and the decrease of myeloid-derived suppressor cells.

CONCLUSIONSRFA can enhance the anti-tumor immunity and effectively inhibit lung metastasis of 4T1 cell-induced breast cancer, and has a good potential effect in the treatment of triple-negative breast cancer and the control of distant metastasis.

Animals ; B-Lymphocytes ; cytology ; CD4-Positive T-Lymphocytes ; cytology ; CD8-Positive T-Lymphocytes ; cytology ; Catheter Ablation ; Female ; Flow Cytometry ; Humans ; Killer Cells, Natural ; cytology ; Lung Neoplasms ; immunology ; prevention & control ; secondary ; Mice ; Mice, Inbred BALB C ; Neoplasm Recurrence, Local ; Triple Negative Breast Neoplasms ; immunology ; pathology ; surgery ; Tumor Burden

Alternatively activated macrophages are more frequently involved in tumor growth, angiogenesis, and immunosuppression. A previous study showed that paeoniflorin, the major active constituent of Paeonia lactiflora Pallas, can inhibit tumor growth and lung metastases of Lewis lung tumor-bearing mice. This study tried to investigate whether paeoniflorin inhibited lung cancer metastasis by inhibiting the alternative activation of macrophages (M2 macrophage). Using a viability assay, the cytotoxicity of paeoniflorin on Lewis lung cancer cells and peritoneal macrophages were investigated. In vitro scratch wound and in vivo lung metastasis experiments were used to test the ability to inhibit the migration of paeoniflorin and the function of M2 macrophages. Flow cytometry was performed to test the cell cycle of Lewis lung cancer cells, and to test the M2 macrophages in peritoneal macrophages and subcutaneous transplantable tumor. It was found that paeoniflorin showed no inhibitory effect on the growth of Lewis lung cancer cells and peritoneal macrophages of mouse in vitro. Paeoniflorin could attenuate the migration of LLC stimulated by alternatively activated macrophages (stimulated for 24 h and 48 h, paeoniflorin 1, 3, 10, 30, 100 μmol·L(-1), P < 0.01 or P < 0.05 vs control group). Paeoniflorin could decrease the cell populations at S phases (paeoniflorin 10, 30, 100 μmol·L(-1), P < 0.05 vs control group) and increase the cell populations at G0-G1 phases of Lewis lung cancer cells (paeoniflorin 100 μmol·L(-1), P < 0.05 vs control group) and reduce the numbers of M2 macrophages in peritoneal macrophages induced by IL-4 (paeoniflorin 1, 3, 10, 30, 100 μmol·L(-1), P < 0.01 vs Control group). Paeoniflorin could reduce lung metastasis of Lewis lung cancer cells xenograft and decrease the numbers of M2 macrophages in subcutaneous xenograft tumour in vivo (paeoniflorin 20, 40 mg·kg(-1), P < 0.01 vs control group). These results suggest that paeoniflorin could reduce lung metastasis of Lewis lung cancer cells xenograft partly through inhibiting the alternative activation of macrophages.
Animals ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Down-Regulation ; drug effects ; Female ; Glucosides ; administration & dosage ; Humans ; Interleukin-4 ; immunology ; Lung Neoplasms ; drug therapy ; immunology ; pathology ; physiopathology ; Macrophages ; cytology ; drug effects ; immunology ; Mice ; Mice, Inbred C57BL ; Monoterpenes ; administration & dosage ; Neoplasm Metastasis ; Paeonia ; chemistry

OBJECTIVETo investigate the effect and mechanism of B16F10-ESAT-6-gpi/IL-21 tumor cell vaccine on pulmonary metastasis in mouse model of melanoma.

METHODSTwelve 8-week old female C57BL/6 mice were used in this study. The mice were injected with wild-type B16F10 cells through tail vein after immunization with B16F10-ESAT-6-gpi/IL-21 tumor cell vaccine, and the pulmonary metastasis was observed. The CD4(+) and CD8(+) T cells were isolated by magnetic activated cell sorting, and then used for the detection of CFSE/7-AAD cytotoxicity by flow cytometry. Serum from the mice immunized with tumor-cell vaccine was used to detect IFN-γ expression by ELISA. The expression of TGF-β2, ZEB1, E-cadherin, and N-cadherin of tumor tissues was detected by RT-PCR and immunofluorescence, respectively.

RESULTSThe mice vaccinated with B16F10-ESAT-6-gpi/IL-21 had significantly fewer nodules in the lung and lower lung weight [(285.8 ± 19.01) mg vs. (406.3 ± 27.12) mg], with lower levels of TGF-β2, ZEB1 and N-cadherin proteins but higher level of E-cadherin protein within the tumor tissue, as compared with the control mice. Meanwhile, the immunized mice had significantly increased CD8(+) T cell killing activity [(42.62 ± 3.465)% vs. (22.29 ± 1.804)%] and IFN-γ expression level [(55.200 ± 7.173) pg/ml vs. (6.435 ± 1.339) pg/ml] over the control mice.

CONCLUSIONSThe B16F10-ESAT-6-gpi/IL-21 vaccine can inhibit the metastasis of melanoma in the lung in vaccinated melanoma-bearing mice. This inhibitory effect is associated with CD8(+) T cell immune response and a higher level of IFN-γ, which may influence on the mesenchymal-epithelial transition of tumor cells.

Animals ; CD8-Positive T-Lymphocytes ; immunology ; Cadherins ; metabolism ; Cancer Vaccines ; immunology ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition ; Female ; Homeodomain Proteins ; metabolism ; Humans ; Interferon-gamma ; metabolism ; Interleukins ; immunology ; Lung ; pathology ; Lung Neoplasms ; metabolism ; secondary ; Melanoma ; metabolism ; pathology ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Organ Size ; Transcription Factors ; metabolism ; Transforming Growth Factor beta2 ; metabolism ; Zinc Finger E-box-Binding Homeobox 1

This study is to optimize the preparation process of fusion protein Fv-LDP which was expressed in the form of inclusion body and consisted of lidamycin apoprotein LDP and single-chain Fv antibody (scFv) directed against type IV collagenase. The preparation and the dissolution of inclusion body, the immobilized metal affinity chromatography of the target protein and the renaturization by stepwise dialysis were optimized by single-factor analysis or orthogonal design. In addition, the refolded fusion protein Fv-LDP was refined by Sephadex G-75 chromatography followed by fluorescence-activated cell sorter (FACS)-based saturation binding assay to measure its antigen-binding activity. After optimization of the process, the purity of fusion protein Fv-LDP existed in the inclusion body was 63.9% and the corresponding solubility was 95.7%; Under denaturing conditions, the purity of fusion protein Fv-LDP was more than 95% after the purification process. The percentage of monomeric fusion protein Fv-LDP was 60% after the refolding process, while it was further refined to 85% which was 5.6-fold higher than that of the initial refolding condition. The refined fusion protein Fv-LDP could bind to human lung adenocarcinoma PAa cells and human hepatoma BEL-7402 cells with the dissociation constants (Kd) of 0.176 micromol x L(-1) and 0.904 micromol x L(-1), respectively. The preparation process of fusion protein Fv-LDP has been successfully optimized, which provides the experimental basis for the production and future development of fusion protein Fv-LDP, and might serve as a relatively practical system for the preparation of other scFv-based proteins expressed in the form of inclusion body.
Adenocarcinoma ; metabolism ; pathology ; Aminoglycosides ; chemistry ; metabolism ; Antibiotics, Antineoplastic ; chemistry ; metabolism ; Apoproteins ; chemistry ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Collagenases ; immunology ; Enediynes ; chemistry ; metabolism ; Escherichia coli ; chemistry ; metabolism ; Humans ; Inclusion Bodies ; chemistry ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; Lung Neoplasms ; metabolism ; pathology ; Protein Binding ; Recombinant Fusion Proteins ; chemistry ; metabolism ; Single-Chain Antibodies ; chemistry ; metabolism

OBJECTIVETo evaluate the immunohistochemical detection of epidermal growth factor receptor(EGFR) mutations using two EGFR mutation-specific monoclonal antibodies: delE746-A750 and L858R.

METHODSA total of 175 paraffin-embedded lung adenocarcinoma tissue samples previously genotyped by directive DNA sequencing were subject to immunostaining using delE746-A750 and L858R antibodies.

RESULTSThere was no significant difference of mutation detection between DNA sequence analysis and delE746-A750 and/or L858R immunostaining (33.7% vs 30.9%, P > 0.05). The overall sensitivity, specificity, positive predictive value and negative predictive value of immunostaining using these two EGFR mutation-specific antibodies were 83.1%, 95.7%, 90.7% and 90.9%, respectively.

CONCLUSIONWith high sensitivity and good specificity, immunohistochemistry using EGFR mutation-specific monoclonal antibodies is an adequate, easy and cost-effective prescreening method to detect EGFR mutations using paraffin-embedded tissue specimens of lung adenocarcinomas.

Adenocarcinoma ; genetics ; metabolism ; pathology ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; DNA Mutational Analysis ; Female ; Gene Deletion ; Humans ; Immunohistochemistry ; Lung Neoplasms ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; Paraffin Embedding ; Point Mutation ; Receptor, Epidermal Growth Factor ; genetics ; immunology ; metabolism ; Sensitivity and Specificity

OBJECTIVETo study the relationship between Chinese medical syndrome types of bronchioloalveolar carcinoma (BAC) and Th1/Th2.

METHODSTotally 60 BAC patients were syndrome typed as qi and yin deficiency syndrome (QYDS) and qi stagnation and phlegm-blood stasis syndrome (QSPSS), 30 cases in each group. Meanwhile, 30 subjects with benign pulmonary nodules were recruited as the control group. The contents of interferon-gamma (INF-gamma), interleukin 4 (IL-4), IL-2, and IL-5 were detected using thoracoscopic technique.

RESULTSAs for Th1 (INF-gamma and IL-2), it was ranked from high to low as the control group > the QSPSS group > the QYDS group (P < 0.05). As for Th2 (IL-4 and IL-5), it was ranked from high to low as the QYDS group > the QSPSS group >the control group (P < 0.05). As for Th1/Th2 (INF-gamma/lL-4, IL-2/IL-5), it was ranked from high to low as the control group > the QSPSS group >the QYDS group (P < 0.05).

CONCLUSIONSCompared with the tissue of benign nodules, Th1 function in tumor tissue of BAC patients was weaker and Th2 function stronger. Chinese medical syndrome types of BAC had correlation with Th1/Th2. Patients of excess syndrome had stronger immunity with Th1/Th2 shifting left,while those of deficiency syndrome were predispose to humoral immunity with Thl/Th2 shifting right.

Adenocarcinoma, Bronchiolo-Alveolar ; diagnosis ; immunology ; pathology ; Adult ; Aged ; Female ; Humans ; Lung Neoplasms ; diagnosis ; immunology ; pathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Th1 Cells ; immunology ; Th1-Th2 Balance ; Th2 Cells ; immunology