IFN-α/β/IFN-γ/IL-15 pathways identify GBP1-expressing tumors with an immune-responsive phenotype.

Immunotherapy is widely used in cancer treatment; however, only a subset of patients responds well to it. Significant efforts have been made to identify patients who will benefit from immunotherapy. Successful anti-tumor immunity depends on an intact cancer-immunity cycle, especially long-lasting CD8 T-cell responses.

Biological characteristics and clinical treatment of pulmonary sarcomatoid carcinoma: a narrative review.

Background And Objective: Pulmonary sarcomatoid carcinoma (PSC) is a subset of non-small cell lung cancer (NSCLC) with highly malignant, aggressive, and heterogeneous features. Patients with this disease account for approximately 0.1-0.

Pre-hepatectomy dynamic circulating tumor DNA to predict pathologic response to preoperative chemotherapy and post-hepatectomy recurrence in patients with colorectal liver metastases.

Objective: To evaluate the predictive value of pre-hepatectomy dynamic circulating tumor DNA (ctDNA) on pathologic response to preoperative chemotherapy and recurrence after liver resection for colorectal liver metastases (CRLM).

Background: Pathologic response is a predictor of clinical outcomes for patients undergoing hepatectomy for CRLM. Postoperative ctDNA has been proven to be sensitive for recurrence detection.

Circulating tumor DNA and tissue complementarily detect genomic alterations in metastatic hormone-sensitive prostate cancer.

The clinical utility of circulating tumor DNA (ctDNA) in hormone-sensitive prostate cancer (HSPC) remains inadequately elucidated. This study presents the largest real-world cohort to conduct a concordance analysis between ctDNA and tissue-based genomic profiling in HSPC patients. The findings reveal diminished ctDNA abundance in cases with low tumor burden and demonstrate an increased concordance rate between ctDNA and tissue along with the progression of disease burden.

Heterogeneity of the tumor immune microenvironment and clinical interventions.

The tumor immune microenvironment (TIME) is broadly composed of various immune cells, and its heterogeneity is characterized by both immune cells and stromal cells. During the course of tumor formation and progression and anti-tumor treatment, the composition of the TIME becomes heterogeneous. Such immunological heterogeneity is not only present between populations but also exists on temporal and spatial scales.

Declaration: Novel SLC3A1 mutation in a cystinuria patient with xanthine stones: a case report.

Background: Cystinuria and xanthinuria are both rare genetic diseases involving urinary calculi. However, cases combining these two disorders have not yet been reported.

Case Presentation: In this study, we report a case of cystinuria with xanthine stones and hyperuricemia.

Recurrence Prediction by Circulating Tumor DNA in the Patient with Colorectal Liver Metastases After Hepatectomy: A Prospective Biomarker Study.

Background: The recurrence rate after hepatic resection of colorectal liver metastases (CRLM) remains high. This study aimed to investigate postoperative circulating tumor DNA (ctDNA) based on ultra-deep next-generation sequencing (NGS) to predict patient recurrence and survival.

Methods: Using the high-throughput NGS method tagged with a dual-indexed unique molecular identifier, named the CRLM-specific 25-gene panel (J25), this study sequenced ctDNA in peripheral blood samples collected from 134 CRLM patients who underwent hepatectomy after postoperative day 6.

Chromothripsis is correlated with reduced cytotoxic immune infiltration and diminished responsiveness to checkpoint blockade immunotherapy.

Chromothripsis caused massive, clustered genomic rearrangements is prevalent in cancer and is considered a new paradigm for tumorigenesis and progression. In this study, we investigated the association among chromothripsis, anti-tumor immune responses, and responsiveness to immune checkpoint blockade (ICB). Quantification of immune cell infiltration and functional enrichment of immune-related signaling pathways were performed in the discovery set (n = 9403) and the validation set (n = 1140).

CD200 cytotoxic T lymphocytes in the tumor microenvironment are crucial for efficacious anti-PD-1/PD-L1 therapy.

Anti-PD-1/PD-L1 therapy, either by anti-PD-1 antibody or anti-PD-L1 antibody, has efficacy by reinvigorating tumor-infiltrating CD8 T cells in a subset of patients with cancer, but it has unequal effects on heterogeneous CD8 T cell populations. Hence, the subset crucial to efficacious PD-1 blockade therapy remains elusive. Here, we found an increase in tumor-infiltrating CD200 cytotoxic T lymphocytes (CTLs) upon PD-1/PD-L1 blockade, with higher proportions of CD200 T cells positively related to a favorable clinical outcome to anti-PD-1/PD-L1 therapy in three independent cohorts of patients with cancer.

Tumor-induced erythroid precursor-differentiated myeloid cells mediate immunosuppression and curtail anti-PD-1/PD-L1 treatment efficacy.

Despite the unprecedented success of immune checkpoint inhibitors (ICIs) as anti-cancer therapy, it remains a prevailing clinical need to identify additional mechanisms underlying ICI therapeutic efficacy and potential drug resistance. Here, using lineage tracking in cancer patients and tumor-bearing mice, we demonstrate that erythroid progenitor cells lose their developmental potential and switch to the myeloid lineage. Single-cell transcriptome analyses reveal that, notwithstanding quantitative differences in erythroid gene expression, erythroid differentiated myeloid cells (EDMCs) are transcriptionally indistinguishable from their myeloid-originated counterparts.

Somatostatin Receptor 2: A Potential Predictive Biomarker for Immune Checkpoint Inhibitor Treatment.

Somatostatin receptor 2 (), the most abundant receptor of somatostatin (), possesses immunoreactivity and is altered in many cancers. However, the association between and efficacy of immune checkpoint inhibitors (ICIs) has not yet been reported. Immunohistochemistry (IHC) information across 20 cancers was collected from the Human Protein Atlas (HPA) and used to analyze the expression of .

Platinum-Based Neoadjuvant Chemotherapy Before Radical Prostatectomy for Locally Advanced Prostate Cancer With Homologous Recombination Deficiency: A Case Report.

More emerging evidence showed that homologous recombination (HR) defect (HRD) may predict sensitivity to platinum agents in metastatic prostate cancer (PCa). Platinum-based neoadjuvant chemotherapy for PCa with HRD has not been reported. Here, we reported a man diagnosed as locally advanced PCa with high Gleason Score (5 + 5) and low PSA level (5.

ENPEP as a potential predictor of immune checkpoint inhibitor efficacy.

Background: The gene ENPEP encodes glutamyl aminopeptidase, which can cut N-terminal aspartic acid from angiotensin II, and is related to tumorigenesis and immune microenvironment, however, the association between the expression of ENPEP and benefits of immune checkpoint inhibitors (ICIs) has had no investigation.

Methods: We assess the immunotherapeutic predictive performance of ENPEP expression and mutation in multiple cohorts, including one discovery cohort (Pender cohort), four validation cohorts (Hugo cohort; Liu cohort; Mariathasan cohort; Zhao cohort), and one mutation cohort (Miao cohort). Cohorts from The Cancer Genome Atlas (TCGA) were used to explore mechanism and analysis prognosis.

Programmed Cell Death Protein Ligand 2 Is a Potential Biomarker That Predicts the Efficacy of Immunotherapy.

Immune checkpoint inhibitor (ICI) responses vary, and biomarkers for predicting responders are urgently needed. Growing evidence points to the association between programmed cell death protein ligand 2 (PDL2) and ICI benefits, while clinical evidences were lacking. Thus, we consolidated five public ICI-treated cohorts to investigate the association between PDL2 expression and ICI treatment prognosis.

Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma.

TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare and heterogeneous subtype of kidney cancer with no standard treatment for advanced disease. We describe comprehensive molecular characteristics of 63 untreated primary TFE3-tRCCs based on whole-exome and RNA sequencing. TFE3-tRCC is highly heterogeneous, both clinicopathologically and genotypically.

A novel germline BRCA2 mutation in a Chinese patient with prostate cancer sensitive to platinum chemotherapy: a case report.

Background: Germline BRCA2 mutation is associated with an aggressive prostate cancer phenotype and indicates higher risk for hereditary cancer. Recently, numerous studies have attempted to identify the genomic landscape of prostate cancer to better understand the genomic drivers of this disease and look for the molecular targets to guide treatment selection.

Case Presentation: We report a 67-year-old patient diagnosed with prostate cancer who experienced rapid disease progression after androgen deprivation therapy and subsequent docetaxel treatment.

Characterization of genomic alterations in Chinese colorectal cancer patients with liver metastases.

Background: The exploration of genomic alterations in Chinese colorectal liver metastasis (CRLM) is limited, and corresponding genetic biomarkers for patient's perioperative management are still lacking. This study aims to understand genome diversification and complexity that developed in CRLM.

Methods: A custom-designed IDT capture panel including 620 genes was performed in the Chinese CRLM cohort, which included 396 tumor samples from metastatic liver lesions together with 133 available paired primary tumors.

A Muscle-Invasive Bladder Cancer Patient With High Tumor Mutational Burden and RB1 Mutation Achieved Bladder Preservation Following Chemotherapy Combined With Immunotherapy: A Case Report.

Neoadjuvant chemotherapy followed by radical cystectomy is the standard of care for patients diagnosed with muscle-invasive bladder cancer (MIBC). However, urinary diversion following radical cystectomy significantly reduces patient quality of life. In addition, patients who significantly respond to neoadjuvant chemotherapy have a strong will to preserve the bladder.

Exploration of the Tumor-Suppressive Immune Microenvironment by Integrated Analysis in -Mutant Lung Adenocarcinoma.

Background: Clinical evidence has shown that few non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor () mutations can benefit from immunotherapy. The tumor immune microenvironment (TIME) is a significant factor affecting the efficacy of immunotherapy. However, the TIME transformational process in -mutation patients is unknown.

ATR and BRCA2 Simultaneous Mutation in a ccRCC With Sarcomatoid Differentiation and Extensive Metastases: A Case Report.

The genomic landscape and driver-gene mutations differ significantly among diverse histological subtypes of clear cell renal cell carcinoma (ccRCC) due to the intratumoral heterogeneity. Frequent mutations in canonical DNA damage response genes, such as BRCA1/2 or ATR serine/threonine kinase (ATR) haven't been reported even in large-scale genomic profiling of ccRCC researches. Herein, we reported a rare ccRCC harboring ATR and BRCA2 simultaneous mutation with complicated morphologies and extensive metastases.

Robust Prediction of Immune Checkpoint Inhibition Therapy for Non-Small Cell Lung Cancer.

Background: The development of immune checkpoint inhibitors (ICIs) is a revolutionary milestone in the field of immune-oncology. However, the low response rate is the major problem of ICI treatment. The recent studies showed that response rate to single-agent programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibition in unselected non-small cell lung cancer (NSCLC) patients is 25% so that researchers defined several biomarkers to predict the response of immunotherapy in ICIs treatment.

Titin mutation in circulatory tumor DNA is associated with efficacy to immune checkpoint blockade in advanced non-small cell lung cancer.

Background: Only a fraction of patients with advanced non-small cell lung cancer (NSCLC) respond well to immune checkpoint blockade (ICB) therapy. Here, we investigated whether Titin () mutation, which has been demonstrated to be a predictive biomarker in tissue-based analysis, can identify patients with a greater likelihood in response to ICB based on circulatory tumor DNA (ctDNA) sequencing.

Methods: In this retrospective analysis, 92 patients with advanced NSCLC from two independent cohorts who received ICB treatment were included.

Mutated DNA Damage Repair Pathways Are Prognostic and Chemosensitivity Markers for Resected Colorectal Cancer Liver Metastases.

Deficiency of the DNA damage repair (DDR) signaling pathways is potentially responsible for genetic instability and oncogenesis in tumors, including colorectal cancer. However, the correlations of mutated DDR signaling pathways to the prognosis of colorectal cancer liver metastasis (CRLM) after resection and other clinical applications have not been fully investigated. Here, to test the potential correlation of mutated DDR pathways with survival and pre-operative chemotherapy responses, tumor tissues from 146 patients with CRLM were collected for next-generation sequencing with a 620-gene panel, including 68 genes in 7 DDR pathways, and clinical data were collected accordingly.

Radiation-induced eosinophils improve cytotoxic T lymphocyte recruitment and response to immunotherapy.

The efficacy of cancer immunotherapy is dictated by CD8 T cell infiltration and the nature of the tumor microenvironment (TME). By inflaming the TME to favor CD8 T cell immunity, radiation is now widely considered as a neoadjuvant for immunomodulation. Here, we observed that local irradiation enhances the infiltration of intratumoral eosinophils, and depletion of eosinophil dampens CD8 T cell infiltration and diminishes the anti-tumor effectiveness of radiation.

Integration of the Tumor Mutational Burden and Tumor Heterogeneity Identify an Immunological Subtype of Melanoma With Favorable Survival.

The tumor mutational burden (TMB) has been reported as a predictive marker of the response to immune checkpoint inhibition (ICI) therapy in previous melanoma clinical trials. However, the TMB alone is not sufficient to accurately predict immunotherapy benefit. Additional biomarkers are needed for better stratification of immunotherapy-sensitive patients.