[Tumor-associated Macrophage: 
Emerging Targets for Modulating the Tumor Microenvironment].

Tumor-associated macrophage (TAM) play a crucial role in the immune microenvironment of lung cancer. Through changes in their phenotype and phagocytic functions, TAM contribute to the initiation and progression of lung cancer. By promoting the formation of an immune-suppressive microenvironment and accelerating the growth of abnormal tumor vasculature, TAM facilitate the invasion and metastasis of lung cancer. Macrophages can polarize into different subtypes with distinct functions and characteristics in response to various stimuli, categorized as anti-tumor M1 and pro-tumor M2 types. In tumor tissues, TAM typically polarize into the alternatively activated M2 phenotype, exhibiting inhibitory effects on tumor immunity. This article reviews the role of anti-angiogenic drugs in modulating TAM phenotypes, highlighting their potential to reprogram M2-type TAM into an anti-tumor M1 phenotype. Additionally, the functional alterations of TAM play a significant role in anti-angiogenic therapy and immunotherapy strategies. In summary, the regulation of TAM polarization and function opens up new avenues for lung cancer treatment and may serve as a novel target for modulating the immune microenvironment of tumors.
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Prognostic implications of neutrophil-to-lymphocyte ratio in patients with extensive-stage small cell lung cancer receiving chemoimmunotherapy: A multicenter, real-world study.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are closely related to the prognosis of patients with non-small cell lung cancer, but their effect on extensive-stage small cell lung cancer (ES-SCLC) remains uncertain. METHODS: This retrospective study was conducted in ES-SCLC patients treated with first-line atezolizumab or durvalumab and platinum-etoposide. Clinical data from three hospitals were analyzed. Significant risk factors for survival were identified using descriptive statistics and Cox regression. Homogeneity was assessed using t-tests or nonparametric tests. Kaplan-Meier analysis revealed an association between high NLR level and median PFS and OS. RESULTS: A total of 300 ES-SCLC patients were included in the study. Cox regression analysis revealed that an elevated NLR level after the second treatment cycle (defined as NLRT2) was an independent prognostic factor for survival. Stratifying patients based on median NLRT2 showed significant differences in both PFS (HR: 1.863, 95% CI: 1.62-2.12, p < 0.001) and OS (HR: 2.581, 95% CI: 2.19-3.04, p < 0.001) between NLR ≥ 1.75 and NLR < 1.75 groups. mPFS and mOS were 8.2 versus 6.1 months and 13.7 versus 9.5 months, respectively. NLR was also associated with treatment efficacy and occurrence of irAEs. Further stratification based on NLR and irAEs showed that in the NLR < 1.75 group, patients with irAEs had prolonged mPFS and mOS. In the NLR ≥ 1.75 group, only mPFS showed a significant difference between patients with and without irAEs. CONCLUSION: NLRT2 and irAEs can predict the prognosis of ES-SCLC patients with first-line ES-SCLC receiving PD-L1 inhibitors combined with chemotherapy.

[Research Progress of Immune Checkpoint TIGIT in Lung Cancer Immunotherapy].

T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) is a newly discovered immune checkpoint molecule, mainly expressed on the surface of T cells and natural killer (NK) cells. By binding to cluster of differentiation 155 (CD155) and other ligands, it inhibits T cell and NK cell-mediated immune responses and affects the tumor microenvironment. Multiple preclinical studies have demonstrated that the TIGIT/CD155 pathway plays a role in a variety of solid and hematological tumors. Clinical trials investigating TIGIT inhibitors alone or in combination with programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors for lung cancer are currently underway.
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[Two Cases of TKI-resistant Small Cell Lung Cancer Transformation 
in Advanced Adenocarcinoma and Literature Review].

Treatment of advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can achieve good disease control, but it will inevitably produce drug resistance. About 3%-10% of the resistance mechanism is small cell transformation. Two cases of stage IV lung adenocarcinoma with EGFR mutation were reported and the disease was controlled after EGFR-TKIs treatment. In case 1, progression-free survival (PFS) before small cell carcinoma transformation was 16 months, and in case 2, PFS before small cell carcinoma transformation was 24 months. Subsequent biopsy after disease progression indicated a shift to small cell lung cancer. Case 1 PFS after small cell carcinoma transformation was 6 months, and case 2 PFS after small cell carcinoma transformation was 8 months, and overall survival (OS) was 36 months, which significantly prolonged the patient's survival. At the same time, the literature of such drug resistance mutations was reviewed. For patients with advanced NSCLC with sensitive mutations, it is necessary to conduct secondary histopathological tests after TKIs treatment resistance, and select subsequent treatment according to different resistance mechanisms for the whole course of disease management.
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