Macrophages are one of the most important cells in the innate immune system, they are converted into two distinct subtypes with completely different molecular phenotypes and functional features under different stimuli of the microenvironment: M1 macrophages induced by IFN-γ/lipopolysaccharides(LPS) and M2 macrophages induced by IL-4/IL-10/IL-13. Tumor-associated macrophages (TAMs) differentiate from macrophages through various factors in the tumor microenvironment (TME). TAMs have the phenotype and function of M2 macrophages and are capable of secreting multiple cytokines to promote tumor progression. Both tumor cells and macrophages can meet the energy needs for rapid cell growth and proliferation through metabolic reprogramming, so a comprehensive understanding of pro-tumor and antitumor metabolic switches in TAM is essential to understanding immune escape mechanisms. This paper focuses on the functions of relevant signaling pathways and cytokines during macrophage polarization and metabolic reprogramming, and briefly discusses the effects of different microenvironments and macrophage pathogenicity, in addition to describing the research progress of inhibitory drugs for certain metabolic and polarized signaling pathways.

Inflammation indicators, such as systemic inflammation response index (SIRI), systemic immune‐inflammation index (SII), neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐lymphocyte ratio (PLR), are associated with poor prognosis in various solid cancers. In this study, we investigated the predictive value of these inflammation indicators in nasopharyngeal carcinoma (NPC). This retrospective study involved 559 patients with NPC and 500 patients with chronic rhinitis, and 255 NPC patients were followed up successfully. Continuous variables and qualitative variables were measured by t test and chi‐square test, respectively. The optimal cut‐off values of various inflammation indicators were determined by receiver operating characteristic (ROC) curve. Moreover, the diagnostic value for NPC was decided by the area under the curves (AUCs). The Kaplan‐Meier methods and the log‐rank test were used to analyse overall survival (OS) and disease‐free survival (DFS). The independent prognostic risk factors for survival and influencing factors of side effects after treatment were analysed by Cox and logistic regression analysis, respectively. Most haematological indexes of NPC and rhinitis were significantly different between the two groups, and PLR was optimal predictive indicators of diagnosis. In the multivariable Cox regression analysis, PLR, WBC, RDW, M stage and age were independent prognostic risk factors. Many inflammation indicators that affected various side effects were evaluated by logistic regression analysis. In conclusion, the combined inflammation indicators were superior to single haematological indicator in the diagnosis and prognosis of NPC. These inflammation indicators can be used to supply the current evaluation system of the TNM staging system to help predict the prognosis in NPC patients.

Inhibitory checkpoint molecules include programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), human endogenous retrovirus-H Long terminal repeat-associating 2 (HHLA2), B7 homolog 4 protein (B7-H4), T cell membrane protein-3 (TIM-3) and Lymphocyte-activation gene 3 (LAG-3), which are up-regulated during tumorigenesis. These pathways are essential to down-regulate the immune system by blocking the activation of T cells. In recent years, immune checkpoint blockers (ICBs) against PD-1, PD-L1, CTLA-4 or TIM-3 has made remarkable progress in the clinical application, revolutionizing the treatment of malignant tumors and improving patients' overall survival. However, the efficacy of ICBs in some patients does not seem to be good enough, and more immune-related adverse events (irAEs) will inevitably occur. Therefore, biomarkers research provides practical guidance for clinicians to identify patients who are most likely to benefit from or exhibit resistance to particular types of immune checkpoint therapy. There are two points in general. On the one hand, given the spatial and temporal differential expression of immune checkpoint molecules during immunosuppression process, it is essential to understand their mechanisms to design the most effective individualized therapy. On the other hand, due to the lack of potent immune checkpoints, it is necessary to combine them with novel biomarkers (such as exosomes and ctDNA) and other anticancer modalities (such as chemotherapy and radiotherapy).

Inflammation and nutritional status have significant effects on the prognosis of cancer patients. This study investigated the predictive value of clinical biochemistry-based indexes in nasopharyngeal carcinoma (NPC). This retrospective study included 559 NPC patients and 500 patients with chronic rhinitis. Continuous variables were measured by t-test. The area under curves (AUC) was used to determine the diagnostic and prognostic value for NPC. Kaplan-Meier methods and the log-rank test were used to analyze overall survival (OS) and disease-free survival (DFS) of the patients. Cox and logistic regression analysis were used to analyze the independent prognostic risk factors for survival and influencing factors of side effects after treatment, respectively. The study results revealed that most indexes of NPC and rhinitis were significantly different between the two groups. In the survival analysis, the systemic inflammation score (SIS), prognostic nutritional index (PNI), albumin/globulin ratio (AGR), albumin (ALB), urea nitrogen (BUN) and creatinine (CREA) had significant influence on the OS and DFS. AGR was the optimal prognostic indicator for NPC. Among these indexes, SIS, AGR, BUN and CERA were independent prognostic factors of OS, AGR and PNI were independent prognostic factors of DFS. Most indexes were risk factors of side effects occurred in radiotherapy. In conclusion, the clinical biochemistry-based indexes, are reliable and of low-cost, therefore, they can be used in predicting diagnosis, prognosis and treatment plans of NPC.

The clinical study of nasopharyngeal carcinoma (NPC) often reveals a large number of lymphocytes infiltrating the primary tumor site. As an important part of the tumor microenvironment, tumor-infiltrating lymphocytes (TILs) do not exist alone but as a complex multicellular population with high heterogeneity. TILs play an extremely significant role in the occurrence, development, invasion and metastasis of NPC. The latest research shows that they participate in tumorigenesis and treatment, and the composition, quantity, functional status and distribution of TILs subsets have good predictive value for the prognosis of NPC patients. TILs are an independent prognostic factor for TNM stage and significantly correlated with better prognosis. Additionally, adoptive immunotherapy using anti-tumor TILs has achieved good results in a variety of solid tumors including NPC. This review evaluates recent clinical and preclinical studies of NPC, summarizes the role of TILs in promoting and inhibiting tumor growth, evaluates the predictive value of TILs, and explores the potential benefits of TILs-based immunotherapy in the treatment of NPC.