TMB (Tumor Mutational Burden)

We also found that tumour-associated macrophages are a source of survival-correlated MHC class II transcripts. Unsupervised learning can facilitate the discovery of biological insight from gene-expression data.

They include larotrectinib/entrectinib/repotrectinib (NTRK fusions), selpercatinib (RET fusions), dabrafenib/trametinib (BRAFV600E mutations), pembrolizumab/dostarlimab (microsatellite instability), pembrolizumab (high tumor mutational burden), and trastuzumab deruxtecan (HER2 3+ expression) (all solid cancers). Pemigatinib is approved for FGFR1-rearranged myeloid/lymphoid neoplasms...For example, BRAFV600E and IDH1/2 mutations; ALK, FGFR, and NTRK fusions; PD-L1 amplification; and CD70 antigens are druggable in both solid and blood malignancies by gene-/immune-targeted therapies/chimeric antigen receptor T cells. Future biomarker-based tissue-agnostic basket studies/approvals should bridge the great divide and include both solid and hematologic cancers.

P1, N=200, Recruiting, BeiGene | Active, not recruiting --> Recruiting | N=37 --> 200 | Trial completion date: May 2026 --> Dec 2026 | Trial primary completion date: May 2025 --> Dec 2026

In each case, checkpoint blockade led to durable radiographic responses. We therefore propose that it is reasonable to assess combined positive score and tumor mutational burden in refractory or recurrent pancreatic cancers when initiation of ICB is being considered.

Furthermore, we present the following two signaling pathways that we have identified: one based on the small G-protein ARF6 driven by KRAS/TP53 mutations, and the other based on the RNA-binding protein Arid5a mediated by inflammatory cytokines, which promote both metabolic reprogramming and immune evasion in pancreatic cancer. Finally, the striking diversity among pancreatic cancers in the relative importance of mutational burden and the tumor microenvironment, their clinical relevance, and the potential for novel therapeutic strategies will be discussed.

This subgroup of IO-responsive NS-pts may have better prognosis. Our findings suggest that DDR-based mutational profiling may help identify NS-pts who could benefit from IO therapy.

Key to immunotherapy efficacy in EC is the tumor's mismatch repair status, with MMR-deficient tumors demonstrating a higher tumor mutational burden and increased PD-L1 expression, making them more susceptible to immune checkpoint inhibitors (ICIs) such as pembrolizumab, durvalumab, and dostarlimab. To overcome resistance in cold tumors, novel therapies, including Chimeric Antigen Receptor (CAR) T cells and tumor-infiltrating lymphocytes are being explored, offering targeted immune-based strategies to enhance treatment efficacy. This review discusses the current understanding of immunotherapy in EC, emphasizing the prognostic and therapeutic implications of MMR status, TME composition, and emerging cell-based therapies.

TBC1D12 5'UTR mutations were significantly associated with older age at diagnosis (60 vs. 46 for wild type, p = 0.003), pathological T3/T4 stage (85.7% vs. 37.7%, p = 0.010), and advanced tumor stages (85.7% vs. 32.5%, p = 0.006) in PTC. This preliminary study for the first time showed a high prevalence of TBC1D12 5'UTR mutations in ATC and indicated an association between TBC1D12 mutation and aggressive characteristics of PTC, which needs to be confirmed in large cohort studies.

The risk score model we developed enhances the prognostication of HCC patients by identifying those at high risk for poor outcomes. This model could lead to new immunotherapy strategies for HCC patients.

Clinically, we assess the utility of THOR in a structured cohort of 238 cancer patients undergoing immunotherapy, supplemented by 2212 patients across 19 subgroups from public datasets. The forecast of the responses and comparison of survival hazards demonstrate that THOR significantly enhances patient stratification and prognostic predictions by incorporating complex immunogenetic biology and subgroup-specific dynamics.

The first systematic exploration of the roles of CRLRs in HBV-HCC demonstrates their critical involvement in the disease's pathogenesis and possible therapeutic implication. The distinct expression patterns and significant biological pathways suggest that these lncRNAs may facilitate novel therapeutic targets.

These findings underscore the critical role of CD19 within the tumor microenvironment, suggesting its potential as a biomarker and a therapeutic target in specific types of cancer.

CHEMBL82047 and CHEMBL381163 are ideal compounds for inhibiting MMP9. The findings of this study will contribute to the design and improvement of MMP9-targeting drugs.

We observed distinct mutation patterns and clinical factors between LUAD and LUSC, and noted that patients with TMB≥10 and PD-L1≥50% exhibited enhanced immunotherapy effects. Combining TMB≥10 and PD-L1≥50% proved to be a more effective predictor of immunotherapy efficacy.

TMB-high (≥10 mut/Mb) was observed in 27% (n = 41) of the patients, with a median age of 75 years for this group. TMB-low (<10 mut/Mb) was observed in 73% (n = 111) of the patients; their median age was 67 years.

Elevated baseline lactate dehydrogenase was linked to shorter PFS. SHR-1701 combined with XELOX and bevacizumab demonstrated a manageable safety profile and potent antitumor activity in unresectable mCRC.

Taken together, these results demonstrate that integrating early changes of ctDNA, normalized bTMB, and the first RECIST response can provide accurate, noninvasive, and early prediction of durable benefits for NSCLC patients treated with ICIs. Further prospective studies are warranted to validate these findings and guide clinical decision-making for optimal immunotherapy in NSCLC patients.

Higher TMB was associated with objective response to ICI, however, TMB was an imperfect biomarker for PFS and OS in our study.

Atirizumab, duvalizumab, atezolizumab, and serplulimab can significantly improve the clinical outcomes of SCLC. Finally, we clarified that the emerging trend of low-dose radiotherapy help overcome the inhibitory signals that limit T-cell infiltration in the tumor matrix. In summary, considering the rapid development of this field, these combined therapy strategies may have unlimited potential to further improve the efficacy of radiotherapy combined with immunotherapy for patients.

This study suggests that immunotherapy is less beneficial in SCC-MU. More work is needed to verify our findings and explore other treatment options.

The automated workflow required one technician vs three technicians to manually prepare the same number of libraries. This study shows, that implementation of the automated TruSight Oncology 500 High-Throughput workflow significantly reduced hands-on time and processing time per sample compared to manual library preparation.

Procarbazine induces a higher mutation burden and novel mutational signatures in patients with Hodgkin lymphoma treated with eBEACOPP and their germline DNA, raising concerns for the genomic health of survivors of Hodgkin lymphoma and hereditary consequences for their offspring. However, replacing procarbazine with dacarbazine appears to mitigate gonadal and stem-cell toxicity while maintaining similar clinical efficacy.

Comprehensive genomic profiling of advanced-stage TOC and UC via WGS reveals key biomarkers and therapeutic targets, enhancing diagnostic accuracy and advancing personalized medicine in gynecological cancers.

We further discussed the factors determining the efficacy of ICIs in EGFR-mutated NSCLC patients, the mutation subtypes and microenvironment characteristics of potential responders. More importantly, we provided insights into areas worth further investigation in the future.

These genomic data highlight the importance of immune infiltration and antigen presentation in dMMR tumors that respond to immune checkpoint blockade. In addition, they suggest that, even within a dMMR population, NGS based measures of MSI could serve as biomarkers of immunotherapy response.

RPS27A overexpression in HCC cells promoted the proliferation, migration, and invasion of cancer cells, and accelerated M2 polarization of macrophage. RPS27A had the potential to be a biomarker for diagnosis, prognosis and immunotherapy response in pan-cancer, and targeting RPS27A may provide new ideas for cancer immunotherapy.

Thus, NCRT does not seem to induce a relevant number of new driver mutations or mutational burden. Genetic profiling implies the potential to support tumor-informed approaches and outcome estimation in future.

Our results indicate that 14-gene RNA-level assay is correlated with specific genetic mutations, including TP53, KRAS, and LRP1B. These insights provide a stronger foundation for integrating molecular risk assessment with clinical and imaging data, offering more comprehensive information to guide more targeted and effective adjuvant therapy strategies in the future management of lung cancer.

These findings hold significant potential to refine treatment strategies, and enhance survival outcomes for NSCLC patients. By enabling a personalized therapeutic approach tailored to individual risk scores, this model may facilitate more precise decisions concerning immunotherapy and chemotherapy, thereby optimizing patient management and treatment efficacy.

The ability of MLTS to predict patient outcomes and its association with key genomic and cellular features underscore its potential as a target for personalized therapy. Future research may focus on integrating MLTS with additional molecular signatures to enhance its clinical application in precision oncology.

We attempted to elucidate the underlying causes and mechanisms behind this lack of response, and to provide new insights into treatment options for these patients. Mutations of key genes within tumor-related signaling pathways and the infiltration of CD8+T cells in the tumor microenvironment may influence the efficacy of immunotherapy for MSI-H solid tumors.

In summary, our study found that DHX34 is highly expressed in pan-cancer and has diagnostic and prognostic value. Targeting DHX34 may improve the therapeutic efficacy of immunotherapy and chemotherapy in a multitude of tumors.

P2, N=80, Recruiting, Dan Zandberg | Trial completion date: Sep 2027 --> Sep 2026 | Trial primary completion date: May 2027 --> May 2026

P1, N=7, Active, not recruiting, National Cancer Institute (NCI) | N=37 --> 7 | Trial completion date: Nov 2024 --> Dec 2025

These findings indicate that GFPT1 is a novel prognostic biomarker and a predictive indicator of chemotherapy response in invasive breast carcinoma. GFPT1 influences mRNA translation, cell cycle regulation, and M2 macrophage infiltration, thereby promoting cancer cell proliferation and metastasis.

This cohort study suggests that indoor tanning exposure, while known to increase risk of melanoma, may not be meaningfully associated with melanoma TMB. Additional characteristics were associated with higher TMB and, thus, potentially improved immune checkpoint inhibitor response.

Our results confirmed that LRP1B affected the efficacy of immunotherapy by modulating the sensitivity of NSCLC cells to ferroptosis. LRP1B mutations represent a highly promising immunotherapeutic biomarker for NSCLC.

Furthermore, the NGFR gene was shown to be more significantly expressed in various pancreatic cancer cells. Bioinformatics analysis was used to create a validated prognostic model of pancreatic cancer, which explored the critical mechanisms of neural-tumor interactions and revealed the potential of cancer-neural crosstalk-related genes as prognostic biomarkers and anti-tumor therapy targets.

Impaired ImmTAC®-redirected cytotoxicity of exhausted T cells was rescued using an anti-PD-1 antibody, supporting the use of a combination strategy to treat tumors with active PDL1-PD1 axes. Our data demonstrate selective and efficient T cell activation and killing by a PRAME-directed TCRxCD3 bispecific, supporting further investigation in multiple cancer indications.

P2, N=28, Not yet recruiting, Shanghai Zhongshan Hospital

P2, N=175, Active, not recruiting, German Cancer Research Center | Recruiting --> Active, not recruiting

This study establishes the prognostic relevance of ARDS-associated genes in LUAD and provides potential biomarkers for personalized therapy and prognosis. Future studies will validate these findings and explore their clinical applications.