Immune evasion and metabolic reprogramming are two fundamental hallmarks of cancer. Interestingly, lactate closely links them together. However, lactate has long been recognized as a metabolic waste product. Lactate and the acidification of the tumor microenvironment (TME) promote key carcinogenesis processes, including angiogenesis, invasion, metastasis, and immune escape. Notably, histone lysine lactylation (Kla) was identified as a novel post-modification (PTM), providing a new perspective on the mechanism by which lactate functions and providing a promising and potential therapy for tumors target. Further studies have confirmed that protein lactylation is essential for lactate to function; it involves important life activities such as glycolysis-related cell functions and macrophage polarization. This review systematically elucidates the role of lactate as an immunosuppressive molecule from the aspects of lactate metabolism and the effects of histone lysine or non-histone lactylation on immune cells; it provides new ideas for further understanding protein lactylation in elucidating lactate regulation of cell metabolism and immune function. We explored the possibility of targeting potential targets in lactate metabolism for cancer treatment. Finally, it is promising to propose a combined strategy inhibiting the glycolytic pathway and immunotherapy.

Purpose: Human papillomavirus-16 (HPV-16) is the most carcinogenic HPV genotype. This study aimed to evaluate the clinical value of POU5F1B and HPV-16-E2/E6 by cervical cytology specimens to predict the cervical intraepithelial neoplasia two grade and more (CIN2+). Methods: Finally, 248 patients with HPV-16 single infection were enrolled. Using cytology specimen by real-time quantitative PCR (qPCR), POU5F1B mRNA and HPV-16-E2/E6 were detected. The relationship of POU5F1B, HPV-16-E2/E6 and CIN2+ were analyzed, and the optimal cut-off values of POU5F1B and HPV-16-E2/E6 to predict CIN2+ were calculated. Results: The mean HPV-16-E2/E6 decreased significantly with cervical lesions development, especially compared with CIN2+ (p< 0.05). And the POU5F1B demonstrated higher expression in CIN2+ than that of normal cervical tissue and CIN1 (p< 0.05). What is more, POU5F1B was negatively correlated with HPV-16-E2/E6. It demonstrated that the area under the receiver operating characteristic curve (AUC) for POU5F1B (0.9058) was higher than that for HPV-16-E2/E6 (0.8983), and the sensitivity and specificity of POU5F1B in the diagnosis of CIN2+ were higher than HPV-E2/E6. Furthermore, it demonstrated that the POU5F1B had the highest odds ratio (OR= 16.84; 95% CI (8.00– 35.46)) for the detection of CIN 2+. Conclusion: HPV-16-E2/E6≤ 0.6471 or POU5F1B≥ 1.0310 in cervical exfoliated cells can be used as a reliable predictor of CIN2+. POU5F1B can be used as a new auxiliary biomarker to determine the HPV infection status and a reliable predictor of CIN2+. The expression of POU5F1B≥ 1.0310 had the highest OR for the detection of CIN2+.

Introduction: The FMS-related tyrosine kinase 3 (FLT3) ligand (FLT3LG), a growth factor, binds to FLT3 on dendritic cell (DCs) to enhance their differentiation and expansion. It has shown great potential as an immunotherapy target for cancers. However, the expression and function of FLT3LG in cervical cancer remain largely unknown. Materials and Methods: In this study, we obtained the expression of FLT3LG, the clinical prognosis in cervical cancer, via multiple databases, including The Cancer Genome Atlas (TCGA), the TISIDB database, and Tumor Immune Estimate Resource (TIMER). The results were further investigated using real-time quantitative PCR (qPCR) cytology specimens in 489 patients. Furthermore, Kaplan-Meier Cox regression and prognostic nomogram analyses were used to assess FLT3LG’s clinical significance in cervical cancer patients. All calculations used the R package. Results: As a result, FLT3LG expression decreased in cervical cancer compared with standard samples. And the low expression of FLT3LG was associated with a poor prognosis. Furthermore, Receiver Operating Characteristics (ROC) analysis indicated that FLT3LG might serve as a valuable diagnostic biomarker for cervical cancer. Additionally, it indicated that the FLT3LG had the highest odds ratio (OR=10.519; (7.371– 27.071)) for detecting CIN 2+. In addition, our result also demonstrated that expression of FLT3LG was closely related to immune cells, immune inhibitors, immunostimulators, receptors, and chemokines in CESC. Conclusion: Research on FLT3LG provided insight into its critical function. Hence, the low expression of FLT3LG may be a valuable biomarker in CESC patients linked with immune infiltration.

Cervical cancer poses a substantial global health challenge. Estrogen-related receptor alpha (ERRα) is a central regulator of cellular energy metabolism associated with poor cancer prognosis. However, the effect of ERRα expression on cervical cancer prognosis and immune infiltration has not been explored. This study aims to clarify the expression pattern and role of ERRα in cervical cancer. We analyzed ERRα expression and its clinical prognosis in cervical cancer using multiple databases, including The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER). The results were further validated through immunohistochemistry (IHC) on 221 cervical cancer tissue samples. Furthermore, Kaplan-Meier and Cox regression analyses were used to assess the clinical significance of ERRα in cervical cancer patients. All calculations were performed using the R package. ERRα expression was significantly higher in cervical cancer tissues compared to normal tissues. High ERRα expression was associated with poor overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). Multivariate Cox regression analysis confirmed ERRα as an independent prognostic factor. Additionally, ERRα expression correlated with various immune cell types and immune checkpoints, indicating its role in the tumor immune microenvironment. ERRα emerges as a promising prognostic biomarker in cervical cancer, influencing immune cell infiltration and potentially guiding personalized therapeutic approaches. Future investigations are warranted to delineate the mechanistic pathways through which ERRα contributes to cervical cancer progression and to assess its viability as a target for innovative immunotherapy strategies.

The effect of cervical cancer immunotherapy is limited. Combination therapy will be a new direction for cervical cancer. Thus, it is essential to discover a novel and available predictive biomarker to stratify patients who may benefit from immunotherapy for cervical cancer. In this study, 563 participants were enrolled. Adenylate cyclase 7 (ADCY7) mRNA was detected by real-time quantitative PCR (qPCR) with cervical cytology specimens. The relationship between ADCY7 and cervical intraepithelial neoplasia in grade 2 and higher (CIN2+) was analyzed, and the optimal cut-off values of the relative expression of ADCY7 mRNA to predict CIN2+ were calculated. In addition, the clinical significance of ADCY7 in cervical cancer was determined by the Kaplan–Meier Cox regression based on the TCGA database. The mean ADCY7 mRNA expression increased significantly with cervical lesion development, especially compared with CIN2+ (p < 0.05). Moreover, the expression of ADCY7 increased significantly in high-risk human papillomavirus (HR-HPV) infection but not in HPV-A5/6 species. The area under the receiver operating characteristic curve (AUC) of ADCY7 was 0.897, and an optimal cut-off was 0.435. Furthermore, ADCY7 had the highest OR (OR= 8.589; 95% CI (2.281–22.339)) for detecting CIN 2+, followed by HPV genotyping, TCT, and age (OR = 4.487, OR = 2.071, and OR = 1.345; 95% CI (1.156–10.518), (0.370–8.137), and (0.171–4.694), respectively). Moreover, this study indicated that higher ADCY7 levels could be a suitable predictor for poor prognosis in cervical cancer due to immune cell infiltration. A new auxiliary predictor of CIN2+ in cervical cytology specimens is ADCY7 ≥ 0.435. Furthermore, it may be a promising prognosis predictor and potential immunotherapy target for the combined treatment of cervical cancer and possibly further block HR-HPV persistent infection.