Background: Lung cancer is among the most common and deadliest malignant tumors worldwide. It is often detected at late stages, resulting in unfavorable outcomes, with tumor cell heterogeneity and medication resistance. Tumor‐associated macrophages are among the key cells contributing to cancer progression. They are categorized into two primary phenotypes: Proinflammatory (M1) and anti‐inflammatory (M2) which are involved in the onset and progression of NSCLC. The role of common cytokines secreted by macrophages in the progression of lung cancer are described, and the effects of various substances such as RNA or protein on the differentiation and polarization of two phenotypes of macrophages are highlighted to characterize the impact of the immune state of tumors on therapeutic effect of treatments and patient prognosis. Researchers have primarily aimed to investigate innovative carriers and strategies based on macrophages to modify the tumor microenvironment.Objectives: These approaches are often integrated with other treatments, particularly immunotherapy, to enhance therapeutic efficacy.Methods: A comprehensive review was carried out by systematically synthesizing existing literature on PubMed, using the combination of the keywords “TAMs”, “NSCLC”, “Drug resistance”, and “therapy”. The available studies were screened for selection based on quality and relevance.Conclusions: TAMs promote tumor invasion, growth, and metastasis by promoting angiogenesis and EMT. In addition, they contribute to the development of drug resistance and the immunosuppressive microenvironment establishment. The immunosuppressive factors secreted by TAM can weaken the activity of immune cells, inhibit their killing effect on tumors, leading to immune suppression and hindering the effectiveness of treatment. Therefore, TAM is a key target for the development of cancer immunotherapy. Various strategies are being explored, including reducing the recruitment of TAMs and influencing their polarization to treat NSCLC. In addition, TAMs based treatment systems can achieve precise delivery of drugs or gene interfering molecules without causing side effects.

Hepatocellular carcinoma (HCC) is the most prevalent type of hepatic carcinoma. Long noncoding RNAs (lncRNAs) are considered crucial regulators of gene expression; however, their functions in HCC are not well understood. Thus, the present study is aimed at elucidating the functions of the lncRNA HOXA-AS3 in HCC. The functions of the HOXA-AS3/miR-455-5p/programmed death-ligand 1 (PD-L1) axis were investigated in vitro via qRT-PCR and dual-luciferase reporter assays. The effect of HOXA-AS3 expression on tumor growth and metastasis was assessed using a mouse xenograft model. High HOXA-AS3 expression was observed in the HCC cell lines. Furthermore, overexpression of HOXA-AS3 in HCC cells enhanced proliferation, migration, and invasion, regulated the cell cycle, and retarded apoptosis. We also identified an miR-455-5p binding site in HOXA-AS3. By sponging miR-455-5p, HOXA-AS3 increased the expression of PD-L1. Additionally, both the inhibition of PD-L1 and overexpression of miR-455-5p reversed the effects on cell proliferation and invasion triggered by the overexpression of HOXA-AS3. In conclusion, HOXA-AS3 modulated the functions of HCC cells through the miR-455-5p/PD-L1 axis. Therefore, HOXA-AS3 may be a novel therapeutic target for HCC.

The tumor microenvironment (TME) is a complex ecosystem with harsh conditions, such as hypoxia, nutrient deprivation, metabolic acidosis and oxidative stress, that promote tumor progression and shape immune responses. In this environment, endoplasmic reticulum stress and the unfolded protein response are activated, with the transcription factor X‑box binding protein 1 (XBP1) serving a key role. XBP1 not only maintains cell protein homeostasis, but also modulates the generation, metabolic adaptation and immunosuppressive function of myeloid‑derived suppressor cells (MDSCs). The TME and tumor‑derived factors, such as exosomes, remotely activate XBP1 in MDSCs, enhancing their survival and immunosuppressive capability by reprogramming lipid and glucose metabolism and upregulating the expression of arginase‑1, inducible nitric oxide synthase, reactive oxygen species and immunosuppressive cytokines. The present review aimed to describe the TME stress‑XBP1‑MDSC‑immunosuppression axis, its molecular mechanisms and the role of XBP1 in MDSC heterogeneity and plasticity. Targeting XBP1 may enhance the efficacy of existing therapies, particularly immune checkpoint blockade, by alleviating MDSC‑mediated immunosuppression, offering a novel paradigm for understanding and reversing tumor immune escape.

The NSABP B-51 trial left unresolved whether postmastectomy radiotherapy benefits ypN0 patients after neoadjuvant chemotherapy. Meanwhile, the PREDICT-DNA study showed that ctDNA clearance after neoadjuvant therapy identifies patients with favorable outcomes irrespective of pathologic response. We propose integrating these datasets: ctDNA status may serve as a tiebreaker for radiotherapy decisions, particularly in patients with residual disease, offering a molecularly guided framework for de-escalation.

Immune checkpoint inhibitors (ICIs) have recently been approved as part of a neoadjuvant therapy plan for triple‑negative breast cancer (TNBC). Consequently, the concurrent use of radiotherapy (RT) and ICIs is becoming increasingly common in clinical practice. Combining RT with ICIs may increase the risk of radiation pneumonitis. However, evidence remains limited regarding whether concurrent ICIs administered during postoperative RT increase the risk of radiation pneumonitis in patients with TNBC. The aim of the present preliminary, single‑centre, retrospective, hypothesis‑generating study was to evaluate the incidence of radiation pneumonitis in patients with TNBC treated with concurrent ICIs and RT. Patients with TNBC, who were treated at Hubei Cancer Hospital (Wuhan, China) between 2022 and 2024, were retrospectively enrolled. The inclusion criteria were receipt of neoadjuvant chemotherapy with or without ICIs, followed by postoperative adjuvant RT. Patients were divided into two groups: Postoperative RT with concurrent ICIs (ICIs‑RT) and postoperative RT alone (RT‑alone group). Baseline clinical characteristics, treatment responses, RT parameters and follow‑up CT scans for the assessment of radiation pneumonitis were documented. The χ² test and Student's t‑test were used for the statistical analyses. A total of 132 patients with TNBC were enrolled. The pathological complete response rate following neoadjuvant therapy was significantly higher in patients who subsequently received postoperative ICIs‑RT than in those who received RT alone (46.7 vs. 22.5%; P=0.01). Of the 132 patients, 30 received ICIs‑RT and 102 received RT alone. In the ICIs‑RT group, 5 patients received pembrolizumab, 22 received tislelizumab, 1 received camrelizumab and 2 received toripalimab. Follow‑up assessments, including contrast‑enhanced CT scans, were performed every 3 months for 1 year. The incidence of grade 1 radiation pneumonitis was 63.3% (19/30) in the ICIs‑RT group and 46.1% (47/102) in the RT‑alone group, with no statistically significant difference between the groups. No grade 2 or higher radiation pneumonitis occurred in either group. Hypothyroidism was observed in 33.3% (10/30) of patients in the ICIs‑RT group, which was significantly higher than the 11.8% (12/102) observed in the RT‑alone group (P=0.01). The incidence of grade 1 radiation dermatitis was 10.0% (3/30) in the ICIs‑RT group and 9.8% (10/102) in the RT‑alone group, whereas the incidence of grade 2 radiation dermatitis was 90.0% (27/30) and 90.2% (92/102), respectively, with no significant difference between the groups. In patients with TNBC previously treated with neoadjuvant ICIs, the addition of concurrent ICIs to postoperative RT did not significantly increase the incidence of radiation dermatitis. Regarding radiation pneumonitis, no statistically significant increase was observed; however, a clinically meaningful trend toward a higher incidence of grade 1 radiation pneumonitis cannot be excluded. An increased risk of hypothyroidism was observed, likely attributable to immune‑related adverse effects of ICIs. These preliminary findings require validation in larger prospective trials.