Purpose: With the progress of cancer immunotherapy, hotspot mutations of common oncogenes and tumor suppressors are becoming new potential therapeutic targets. TP53 R273C mutation is one of the hotspot mutations of TP53, and it has a higher frequency in low-grade glioma (LGG). However, the function of this mutation and its prognostic significance in LGG are not still clear.Methods: To address this question, RNA sequencing, clinical, and SNP data of LGG patients from the TCGA database were downloaded. The Kaplan–Meier (KM) method was used for survival analysis. Immune cell populations in this cohort were assessed via the MCP counter and CIBERSORT. DNA damage/repair scores were calculated by GSVA analysis. WGCNA was conducted to identify genes related to TMB.Results: In the context of IDH1/2 mutation, LGG patients with TP53 R273C mutation had worse prognosis than other mutation types and wild types. This conclusion is still valid in LGG patients who had received chemotherapy or radiotherapy. Considering the 1p19q codeletion status, it was found that patients with both R273C mutation and 1p19q non-codeletion had the worst prognosis. Further analysis showed that LGG patients with TP53 R273C mutation had higher M2 macrophage infiltration and tumor mutation burden (TMB) than that of TP53 wild-type LGG patients, and higher TMB indicates poor prognosis in LGG patients. Furthermore, we identified genes which could be associated with higher M2 macrophage infiltration and TMB in LGG patients with TP53 R273C mutation.Conclusion: The study indicates that TP53 R273C mutation is very likely oncogenic and may be used as an indicator of the prognosis of LGG.

Background Despite the crucial involvement of the EGFR pathway in hepatocellular carcinoma (HCC), the clinical efficacy of EGFR antibodies in HCC remains uncertain. While existing evidence suggests that immune dysfunction and tumor microenvironment alterations may contribute to treatment resistance, the precise mechanisms underlying this phenomenon in HCC warrant further investigation. Methods In this study, we employed patient-derived xenograft (PDX) models generated from 14 HCC patients enrolled in the REHOPE301 cohort to evaluate the sensitivity to nimotuzumab, a humanized anti-EGFR monoclonal antibody. Whole-exome sequencing (WES) and single-cell RNA sequencing were performed on tumor tissues and tumor-infiltrating lymphocytes (TILs) to elucidate the association between TIL characteristics and EGFR antibody response. A predictive risk score and nomogram were subsequently developed using LASSO regression analysis. The prognostic performance of this model was evaluated using 2 external datasets (ICGC-JP and GSE141202) through receiver operator characteristic (ROC) curves and calibration curves analyses. Results Nimotuzumab demonstrated a 50% response rate (7/14) in PDX models. Immune profiling revealed distinct TIL patterns between responders and non-responders. Notably, CD4 ⁺ CCR7 ⁺ T cells were significantly enriched in resistant tumors (p < 0.001) and negatively correlated with the nimotuzumab response (r = -0.767 p = 0.02). In non-responsive tumors, CD4 ⁺ CCR7 ⁺ T cells exhibited interactions with macrophages and CD8 ⁺ PDCD1 ⁺ T cells. A reduced infiltration of CD4 ⁺ CCR7 ⁺ T cells was associated with improved prognosis and enhanced EGFR antibody efficacy across multiple cancer types. Furthermore, a nine-gene signature related to CD4 ⁺ CCR7 ⁺ T cells was identified as a strong prognostic factor in HCC (HR = 5.19, 95% CI: 3.18–8.46, P < 0.001), and was used to construct a nomogram. WES confirmed prognostic gene mutations (VCAN, CAMK4, and CD226) potentially influencing nimotuzumab response. Conclusions Our findings indicate that increased infiltration of central memory CD4 ⁺ CCR7 ⁺ T cells in HCC may reflect an immunosuppressive tumor microenvironment, thereby impairing EGFR antibody efficacy and worsening patient prognosis.