Continuous revision of the histologic and stage-wise classification of lung cancer by the World Health Organization (WHO) provides the foundation for therapeutic advances by promoting molecular targeted and immunotherapies and ensuring accurate diagnosis. Cancer epidemiologic data provide helpful information for cancer prevention, diagnosis, and management, supporting health-care interventions. Global cancer mortality projections from 2016 to 2060 show that cancer will overtake ischemic heart diseases (IHD) as the leading cause of death (18.9 million) immediately after 2030, surpassing non-small cell lung cancer (NSCLC), which accounts for 85 percent of lung cancers. The clinical stage at the diagnosis is the main prognostic factor in NSCLC therapies. Advanced early diagnostic methods are essential as the initial stages of cancer show reduced mortality compared to the advanced stages. Sophisticated approaches to proper histological classification and NSCLC management have improved clinical efficiency. Although immune checkpoint inhibitors (ICIs) and targeted molecular therapies have refined the therapeutic management of late-stage NSCLC, the specificity and sensitivity of cancer biomarkers should be improved by focusing on prospective studies, followed by their use as therapeutic tools. The liquid biopsy candidates such as circulating tumor cells (CTCs), circulating cell-free tumor DNA (cfDNA), tumor educated platelets (TEP), and extracellular vesicles (EVs) possess cancer-derived biomolecules and aid in tracing: driver mutations leading to cancer, acquired resistance caused by various generations of therapeutic agents, refractory disease, prognosis, and surveillance.

Pancreatic ductal adenocarcinoma (PDAC), the fourteenth most common malignancy, is a major contributor to cancer-related death with the utmost case fatality rate among all malignancies. Functional mitochondria, regardless of their complex ecosystem relative to normal cells, are essential in PDAC progression. Tumor cells’ potential to produce ATP as energy, despite retaining the redox potential optimum, and allocating materials for biosynthetic activities that are crucial for cell growth, survival, and proliferation, are assisted by mitochondria. The polyclonal tumor cells with different metabolic profiles may add to carcinogenesis through inter-metabolic coupling. Cancer cells frequently possess alterations in the mitochondrial genome, although they do not hinder metabolism; alternatively, they change bioenergetics. This can further impart retrograde signaling, educate cell signaling, epigenetic modifications, chromatin structures, and transcription machinery, and ultimately satisfy cancer cellular and nuclear demands. To maximize the tumor microenvironment (TME), tumor cells remodel nearby stromal cells and extracellular matrix. These changes initiate polyclonality, which is crucial for growth, stress response, and metastasis. Here, we evaluate all the intrinsic and extrinsic pathways drawn by mitochondria in carcinogenesis, emphasizing the perspectives of mitochondrial metabolism in PDAC progression and treatment.

Despite the progress in the comprehension of LC progression, risk, immunologic control, and treatment choices, it is still the primary cause of cancer-related death. LC cells possess a very low and heterogeneous antigenicity, which allows them to passively evade the anticancer defense of the immune system by educating cytotoxic lymphocytes (CTLs), tumor-infiltrating lymphocytes (TILs), regulatory T cells (Treg), immune checkpoint inhibitors (ICIs), and myeloid-derived suppressor cells (MDSCs). Though ICIs are an important candidate in first-line therapy, consolidation therapy, adjuvant therapy, and other combination therapies involving traditional therapies, the need for new predictive immunotherapy biomarkers remains. Furthermore, ICI-induced resistance after an initial response makes it vital to seek and exploit new targets to benefit greatly from immunotherapy. As ICIs, tumor mutation burden (TMB), and microsatellite instability (MSI) are not ideal LC predictive markers, a multi-parameter analysis of the immune system considering tumor, stroma, and beyond can be the future-oriented predictive marker. The optimal patient selection with a proper adjuvant agent in immunotherapy approaches needs to be still revised. Here, we summarize advances in LC immunotherapy approaches with their clinical and preclinical trials considering cancer models and vaccines and the potential of employing immunology to predict immunotherapy effectiveness in cancer patients and address the viewpoints on future directions. We conclude that the field of lung cancer therapeutics can benefit from the use of combination strategies but with comprehension of their limitations and improvements.

Infection with viruses, bacteria, and parasites are thought to be the underlying cause of about 8–17% of the world’s cancer burden, i.e., approximately one in every five malignancies globally is caused by an infectious pathogen. Oncogenesis is thought to be aided by eleven major pathogens. It is crucial to identify microorganisms that potentially act as human carcinogens and to understand how exposure to such pathogens occur as well as the following carcinogenic pathways they induce. Gaining knowledge in this field will give important suggestions for effective pathogen-driven cancer care, control, and, ultimately, prevention. This review will mainly focus on the major onco-pathogens and the types of cancer caused by them. It will also discuss the major pathways which, when altered, lead to the progression of these cancers.

Background: Despite advances in immunotherapy, non-small-cell lung carcinoma (NSCLC)’s clinical success is limited, possibly due to substantial immunological alterations in advanced cancer patients. This study examines the immunomodulatory effects of sEVs derived from lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) on T cells. Methods: SEVs were isolated from lung cancer cell lines and Jurkat-E6.1. SEV size and morphology were analyzed by NTA and TEM, respectively, while Western blotting confirmed sEV markers. SEV uptake was assessed, followed by resazurin assay, RNA isolation, quantification, cDNA preparation, RT-PCR, nano LC-MS, and bioinformatic analysis, before and after treating Jurkat-E6.1 cells with sEVs from A549 and SKMES1. Results: Cancer-derived sEVs were efficiently internalized by immune cells, reducing T-cell viability. The real-time PCR analysis showed downregulation of KI67, BCL2, BAX, TNFA, IL6, TGFβ, and IL10, suggesting reduced proliferation, dysregulated apoptosis, and impaired inflammatory and immunosuppressive signaling, and the upregulation of GZMB and IL2 suggests retained cytotoxic potential but possibly dysfunctional T-cell activation. Proteomic analysis revealed 39 differentially abundant proteins (DAPs) in ADC-treated T cells and 276 in SCC-treated T cells, with 19 shared DAPs. Gene Ontology (GO) analysis of these DAPs highlighted processes such as sEV biogenesis, metabolic pathways, and regulatory functions, with ADC sEVs influencing NAD metabolism, ECM binding, and oxidoreductase activity, while SCC sEVs affected mRNA stability, amino acid metabolism, and cadherin binding. The cytoplasmic colocalization suggests the presence of these proteins in the cellular and extracellular lumen, indicating the potential of further release of these proteins in the vesicles by T cells. Conclusion: Lung cancer-derived sEVs regulate T-cell activities through immunoregulatory signaling. The molecular interactions between sEVs and immune cells can reveal novel tumor immune regulatory mechanisms and therapeutic targets.