The heterogeneity of tumor-associated macrophages and strategies to target it

Tumor-associated macrophages(TAMs)are emerging as targets for tumor therapy because of their primary role in promoting tumor progression.Several studies have been conducted to target TAMs by reducing their infiltration,depleting their numbers,and reversing their phenotypes to suppress tumor progression,leading to the development of drugs in preclinical and clinical trials.However,the heterogeneous characteristics of TAMs,including their ontogenetic and functional heterogeneity,limit their targeting.Therefore,in-depth exploration of the heterogeneity of TAMs,combined with immune checkpoint therapy or other therapeutic modalities could improve the efficiency of tumor treatment.This review focuses on the heterogeneous ontogeny and function of TAMs,as well as the current development of tumor therapies targeting TAMs and combination strategies.

Targeting tumor microenvironment for non-small cell lung cancer immunotherapy

The tumor microenvironment(TME)is composed of different cellular and non-cellular elements.Constant inter-actions between tumor cells and the TME are responsible for tumor initiation,tumor progression,and responses to therapies.Immune cells in the TME can be classified into two broad categories,namely adaptive and innate immunity.Targeting these immune cells has attracted substantial research and clinical interest.Current research focuses on identifying key molecular players and developing targeted therapies.These approaches may offer more efficient ways of treating different cancers.In this review,we explore the heterogeneity of the TME in non-small cell lung cancer,summarize progress made in targeting the TME in preclinical and clinical studies,discuss the potential predictive value of the TME in immunotherapy,and highlight the promising effects of bispecific antibodies in the era of immunotherapy.

Subsequent strategies and underlying mechanism of acquired resistance to PD-1 axis inhibitors in advanced non-small cell lung cancer

To the Editor:With the widespread application of immune checkpoint inhibitors(ICIs)in clinical practice,acquired resistance(AR)to programmed death-1(PD-1)/programmed death ligand 1(PD-L1)axis inhibitors in advanced nonsmall cell lung cancer(NSCLC)develops and limits the durability of immunotherapy.AR is a clinical condition in which a patient initially responds to ICIs but relapses and progresses after a period of time.The rates of AR have not been routinely reported in lung cancer but typically range from 12.9%to 64%.[1]However,studies on subsequent management strategies and the mechanism of AR to PD-1/PD-L1 axis inhibitors in lung cancer are limited.The main exploratory strategies are immunotherapy rechallenge and the combination of ICIs with other therapies,including local therapy,chemotherapy,antiangiogenetic treatment,and cytotoxic T lymphocyte antigen 4(CTLA-4)inhibitors.[2]The purpose of this study was to characterize the clinical patterns of AR and compare different subsequent therapies and outcomes in NSCLC patients after AR to PD-1/PD-L1 inhibitors.Moreover,we explored the underlying mechanism of AR by analyzing the alterations in next-generation sequencing(NGS)data before and after AR.

High-throughput single-сell sequencing in cancer research

With advances in sequencing and instrument technology,bioinformatics analysis is being applied to batches of massive cells at single-cell resolution.High-throughput single-cell sequencing can be utilized for multi-omics characterization of tumor cells,stromal cells or infiltrated immune cells to evaluate tumor progression,responses to environmental perturbations,heterogeneous composition of the tumor microenvironment,and complex intercellular interactions between these factors.Particularly,single-cell sequencing of T cell receptors,alone or in combination with single-cell RNA sequencing,is useful in the fields of tumor immunology and immunotherapy.Clinical insights obtained from single-cell analysis are critically important for exploring the biomarkers of disease progression or antitumor treatment,as well as for guiding precise clinical decision-making for patients with malignant tumors.In this review,we summarize the clinical applications of single-cell sequencing in the fields of tumor cell evolution,tumor immunology,and tumor immunotherapy.Additionally,we analyze the tumor cell response to antitumor treatment,heterogeneity of the tumor microenvironment,and response or resistance to immune checkpoint immunotherapy.The limitations of single-cell analysis in cancer research are also discussed.