Bone metastases diminish extraosseous response to checkpoint blockade immunotherapy through osteopontin-producing osteoclasts.

Bone metastatic lesions typically associate with suboptimal responses to immune checkpoint blockade (ICB) therapies. In this study, we observed that across multiple clinical cohorts and a variety of mouse models, the presence of osseous metastases induces ICB resistance in extraosseous tumors. Mechanistically, this long-distance communication is mediated by osseous tumor-conditioned osteoclasts producing osteopontin (OPN).

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.

Pretreatment levels of serum alkaline phosphatase are associated with the prognosis of patients with non‑small cell lung cancer receiving immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have been an encouraging treatment method in non-small cell lung cancer (NSCLC). However, bone and liver metastases are considered to restrain immunotherapy efficacy. Since serum alkaline phosphatase (ALP) is associated with bone and liver metastases, it was investigated whether serum ALP could be a novel biomarker to predict the efficacy of ICIs treatment.

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).

Prognostic and clinical significance of HER-2 low expression in early-stage gastric cancer.

Introduction: Gastric cancer is the most fifth common tumor worldwide. Human epidermal growth factor receptor 2 (HER2) overexpression is associated with poor prognosis and clinical characteristics in gastric cancer. Nevertheless, the biology of HER2-low expression has not reported in gastric cancer.

Myeloid-Derived Suppressor Cells: A Multifaceted Accomplice in Tumor Progression.

Myeloid-derived suppressor cell (MDSC) is a heterogeneous population of immature myeloid cells, has a pivotal role in negatively regulating immune response, promoting tumor progression, creating pre-metastases niche, and weakening immunotherapy efficacy. The underlying mechanisms are complex and diverse, including immunosuppressive functions (such as inhibition of cytotoxic T cells and recruitment of regulatory T cells) and non-immunological functions (mediating stemness and promoting angiogenesis). Moreover, MDSC may predict therapeutic response as a poor prognosis biomarker among multiple tumors.

Peripheral eosinophil counts predict efficacy of anti-CD19 CAR-T cell therapy against B-lineage non-Hodgkin lymphoma.

The onset of cytokine release syndrome (CRS) and persistence of anti-CD19 chimeric antigen receptor T (CAR-T) cells after infusion correlate with clinical responsiveness. However, there are no known baseline biomarkers that can predict the prognosis of patients with B-lineage non-Hodgkin lymphoma (B-NHL). The aim of this study was to identify blood cell populations associated with beneficial outcomes in B-NHL patients administered CAR-T cell immunotherapies.

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.

Gene expression profiling identified TP53PIK3CA as a potential biomarker for patients with triple-negative breast cancer treated with immune checkpoint inhibitors.

Triple-negative breast cancer (TNBC) accounts for 15-30% of all breast cancer cases and is clinically difficult to treat due to the lack of hormone or human epidermal growth factor receptor 2 receptors, which are usually targeted by the most successful therapeutic approaches. Immune checkpoint inhibitors (ICIs) have offered long-term survival benefits in several types of solid tumors, however with low response rates. Thus, there is an urgent need to develop feasible biomarkers for identifying patients with TNBC, who are responsive.

Immune Landscape of Colorectal Cancer Tumor Microenvironment from Different Primary Tumor Location.

To define differences in tumor microenvironment (TME) immune phenotypes between right and left colorectal cancers (CRCs) and explore their therapeutic implications. Gene expression profiling and clinical characteristics of patients with CRC were retrieved from The Cancer Genome Atlas data portal. Immune cell infiltration was estimated based on single-sample gene set enrichment analysis.

Association between angiogenesis and cytotoxic signatures in the tumor microenvironment of gastric cancer.

Background: A suppressive immune microenvironment and pathological angiogenesis are hallmarks of gastric cancer. Theoretically, immune checkpoint inhibitors (ICIs) stimulate pre-primed neoantigen-specific T cells, and antiangiogenic agents then facilitate their infiltration into the tumor niche by promoting vascular normalization. Currently, the interconnections of these two phenotypes and their relevance to the tumor microenvironment (TME) have not been fully characterized in gastric cancer.

Tumor Microenvironment Properties are Associated With Low CD68-positive Cell Infiltration and Favorable Disease-free Survival in EGFR-mutant Lung Adenocarcinoma.

Background: The benefits of immune checkpoint inhibitors for first-line treatment in patients with lung adenocarcinoma harboring EGFR mutations are unclear. The effects of ICIs depend on the tumor microenvironment (TME). Differences in TME properties between mutant and wild-type EGFR have not been fully characterized.