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Tumor-specific enhanced NIR-II photoacoustic imaging via photothermal and low-pH coactivated AuNR@PNIPAM-VAA nanogel.

BACKGROUND: Properly designed second near-infrared (NIR-II) nanoplatform that is responsive tumor microenvironment can intelligently distinguish between normal and cancerous tissues to achieve better targeting efficiency. Conventional photoacoustic nanoprobes are always "on", and tumor microenvironment-responsive nanoprobe can minimize the influence of endogenous chromophore background signals. Therefore, the development of nanoprobe that can respond to internal tumor microenvironment and external stimulus shows great application potential for the photoacoustic diagnosis of tumor. RESULTS: In…

The Role of Chemokines in Promoting Colorectal Cancer Invasion/Metastasis.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Although most of the primary CRC can be removed by surgical resection, advanced tumors sometimes show recurrences in distant organs such as the liver, lung, lymph node, bone or peritoneum even after complete resection of the primary tumors. In these advanced and metastatic CRC, it is the tumor-stroma interaction in the tumor microenvironment that often promotes cancer invasion and/or metastasis through chemokine signaling. The tumor microenvironment contains numerous host cells that may suppress or promote …

Impact of Immune Cell Heterogeneity on HER2+ Breast Cancer Prognosis and Response to Therapy.

Breast cancer is a heterogeneous disease with a high degree of diversity among and within tumors, and in relation to its different tumor microenvironment. Compared to other oncotypes, such as melanoma or lung cancer, breast cancer is considered a "cold" tumor, characterized by low T lymphocyte infiltration and low tumor mutational burden. However, more recent evidence argues against this idea and indicates that, at least for specific molecular breast cancer subtypes, the immune infiltrate may be clinically relevant and heterogeneous, with significant variations in its stromal cell/protein comp…

Codelivery Nanosystem Targeting the Deep Microenvironment of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is considered as one of the most aggressive malignancies due to its unique microenvironment of which the cardinal histopathological feature is the remarkable desmoplasia of the stroma, taking up about 80% of the tumor mass. The desmoplastic stroma negatively affects drug diffusion and the infiltration of T cells, leading to an immunosuppressive microenvironment. However, this unique microenvironment can limit the physical spread of pancreatic cancer via a neighbor suppression effect. Here, a tumor central stroma targeting and microenvironment responsive

Dissecting the role of bone marrow stromal cells on bone metastases.

Tumor-induced bone disease is a dynamic process that involves interactions with many cell types. Once metastatic cancer cells reach the bone, they are in contact with many different cell types that are present in the cell-rich bone marrow. These cells include the immune cells, myeloid cells, fibroblasts, osteoblasts, osteoclasts, and mesenchymal stem cells. Each of these cell populations can influence the behavior or gene expression of both the tumor cells and the bone microenvironment. Additionally, the tumor itself can alter the behavior of these bone marrow cells which further alters both t

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… Src inhibitors have shown promise in targeting MDSCs by inhibiting their recruitment and MMP-9 gene expression in the tumor microenvironment [ 73 ]. … Stromal cells in tumor microenvironment and breast cancer. Cancer and Metastasis Reviews. 2013;32(1-2):303–315. doi: 10.1007/s10555-012-9415-3. 118. Tchou J, Conejo-Garcia J. …

Unlocking the Promise of Antitumor Hyperthermia-Immunotherapy with Spiky Surface Topology.

Uveal melanoma (UM) is the most prevalent primary intraocular malignant tumor in adults with high mortality rate. Recently, immunotherapy has shown great success in other tumors, however, its therapeutic effect in UM is unsatisfactory, possibly due to the insufficient immune cell infiltration and low immunogenicity of UM. Thus, an efficient therapeutic strategy to reverse the immunosuppressive tumor microenvironment is required. Herein, a PD-L1 modified hierarchical structure consisting of a magnetic Fe3O4 core and spiky silica shell (MNP@Spiky/PD-L1) is developed to reverse the immunosuppress…

Loss of NCCRP1 overcomes immune evasion in lung adenocarcinoma.

BACKGROUND: The low response rate to immunotherapy in patients with lung adenocarcinoma is primarily due to tumor immune evasion. The tumor … equently secrete CXCL9 and CXCL10, enhancing the infiltration of CD8+ T cells and NK cells into the tumor microenvironment. Mechanistically, NCCRP1 and STAU1 competitively bind to NEDD4. NCCRP1 deficiency enhances the STAU1-NEDD4 interaction, promoting ubiquitination and proteasomal degradation of STAU1, thereby increasing CX3CL1 messenger RNA stability. Remarkably, abl …

Harnessing Self-Assembling Peptides on γδ T Cells to Enhance Anti-Tumor Immunity.

γδ T cells possess significant anti-tumor potential; however, the expression of immune checkpoint molecules on tumor cells often leads to functional exhaustion of these T cells, resulting in variable outcomes in clinical trials. Targeting these immune checkpoints may alleviate the inhibitory effects of the tumor microenvironment on γδ T cell functionality. In this study, we developed a PD-L1-targeting peptide conjugated with maleimide, facilitating self-assembly on the surface of γδ T cells to form fibrous structures via Michael addition reactions with thiol groups on the cell membrane. Our fi…

[Melanoma microenvironment-impact of modern therapies].

BACKGROUND: A considerable proportion of patients with advanced melanoma succumb to metastatic disease despite the initial success of modern therapies. OBJECTIVES: An overview of the melanoma tumor microenvironment with special focus on approved therapies and new innovative strategies is given. METHODS: Current clinical trials and scientific insights concerning the impact of the tumor microenvironment on progression and therapy of advanced melanoma are reviewed and discussed. RESULTS: The tumor microenvironment with its manifold components and interactions plays a major role in the treatmen…

Pien-Tze-Huang inhibits colorectal cancer liver metastasis in mice by modulating immunosuppressive and fibrotic microenvironments.

Pien-Tze-Huang (PZH) is a well-known traditional Chinese medicine with anti-inflammation and anti-tumor effects. However, its role in tumor … nhibit liver metastasis of CRC cells in mice by modulating the immune and stromal components of the tumor microenvironment, offering a promising therapeutic strategy for CRC patients with liver metastasis.

Histone lactylation-driven IGF2BP3 promotes intrahepatic cholangiocarcinoma progression via SPP1/CD44-dependent macrophage polarization.

The tumor microenvironment is a critical regulator of cancer progression. Histone lactylation, a novel post-translational modification, has emerged as a key player in various tumors and is closely linked to macrophage polarization within the immune tumor microenvironment. Here, we delineated the signaling axis through which histone lactylation, specifically H3K18la, orchestrates crosstalk between intrahepatic cholangiocarcinoma cells and the tumor microenvironment (TME). Cleavage Under Target and Tagmentation analysis revealed an enrichment of H3K18la at the promoter of the N6-methyladenosine …

CXCR4-targeted lipid nanozymes for metastasis blockade and immune microenvironment reprogramming in hematological malignancies.

Hematological malignancies are characterized by pronounced metastatic potential associated with the chemokine receptor 4/stromal cell-derived factor-1α (CXCR4/CXCL12) signaling axis, high relapse rates, and a profoundly immunosuppressive tumor microenvironment, all of which severely limit the long-term efficacy of existing therapeutic strategies. Herein, we developed a CXCR4-targeted lipid nanozyme platform (Pt-LNP@E5), in which platinum nanozyme catalytic units and E5 peptide were hierarchically integrated to synergistically achieve metastasis blockade and immune microenvironment remodeling. …

Diversity of dynamics and morphologies of invasive solid tumors.

Complex tumor-host interactions can significantly affect the growth dynamics and morphologies of progressing neoplasms. The growth of a confined solid tumor induces mechanical pressure and deformation of the surrounding microenvironment, which in turn influences tumor growth. In this paper, we generalize a recently developed cellular automaton model for invasive tumor growth in heterogeneous microenvironments [Y. Jiao and S. Torquato, PLoS Comput. Biol.7, e1002314 (2011)] by incorporating the effects of pressure. Specifically, we explicitly model the pressure exerted on the growing tumor due t

Interventional therapy for hepatocellular carcinoma in the immunotherapy era: From mechanism exploration to materials innovation.

Hepatocellular carcinoma(HCC) ranks among the leading causes of cancer-related mortality worldwide. In the treatment landscape of HCC, transarterial therapies plfan'yiay a crucial role. This review focuses on transarterial embolization for HCC, with particular emphasis on transarterial chemoembolization(TACE) and transarterial radioembolization(TARE), exploring their significant effects on the tumor microenvironment. TACE involves the liberation of tumor-derived antigens and damage-associated molecular patterns (DAMPs), while exerting direct modulatory influences on immune populations includin…

Cancer therapy targeting the fibrinolytic system.

The tumor microenvironment is recognized as a key factor in the multiple stages of cancer progression, mediating local resistance, immune-escape and metastasis. Cancer growth and progression require remodeling of the tumor stromal microenvironment, such as the development of tumor-associated blood vessels, recruitment of bone marrow-derived cells and cytokine processing. Extracellular matrix breakdown achieved by proteases like the fibrinolytic factor plasmin and matrix metalloproteases is necessary for cell migration crucial for cancer invasion and metastasis. Key components of the fibrinolyt…

Pathological complete response to neoadjuvant chemotherapy may improve antitumor immune response via reduction of regulatory T cells in muscle-invasive bladder cancer.

The prognosis for patients who achieve a pathologic complete response in bladder cancer is excellent, but the association between their prognosis and the tumor microenvironment is unclear. We investigated the tumor immune microenvironment of those with pathological complete response after platinum-based neoadjuvant chemotherapy for cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry. Our retrospective study included 12 patients with pathological complete response who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder c…

Intratumoral lactic acid neutralization strategy for boosting chemoimmunotherapy using liposomal sodium bicarbonate.

Glycolysis-related lactic acid overproduction creates an "ion-trapping" barrier and immunosuppressive tumor microenvironment that compromise effective intratumoral drug delivery and therapy. Therefore, normalization of tumor microenvironment via lactic acid neutralization can be a promising avenue for overcoming this therapeutic hurdle. In this study, the flexible liposomes loaded with sodium bicarbonate (NaHCO3@Flip) were used as a nano-adjuvant to boost chemoimmunotherapy. Their effects on assisting DOXIL and anti-programmed cell death protein 1 (PD-1) therapy were investigated. NaHCO3@Flip …

Molecular biology of bone metastasis.

Metastasis is a final stage of tumor progression. Breast and prostate cancer cells preferentially metastasize to bone, wherein they cause incurable osteolytic and osteoblastic lesions. The bone matrix is rich in factors, such as transforming growth factor-beta and insulin-like growth factors, which are released into the tumor microenvironment by osteolysis. These factors stimulate the growth of tumor cells and alter their phenotype, thus promoting a vicious cycle of metastasis and bone pathology. Physical factors within the bone microenvironment, including low oxygen levels, acidic pH, and hig…

Peritoneal Microenvironment Promotes Appendiceal Adenocarcinoma Growth: A Multi-omics Approach Using Patient-Derived Xenografts.

UNLABELLED: Appendiceal adenocarcinoma (AA) is unique from other gastrointestinal malignancies in that it almost exclusively metastasizes to the peritoneal cavity. However, few studies have investigated the molecular interaction of the peritoneal microenvironment and AA. Here, we use a multi-omics approach with orthotopic and flank-implanted patient-derived xenografts (PDX) to study the effect of the peritoneal microenvironment on AA. AA tumors implanted in the peritoneal microenvironment tended to grow faster and displayed greater nuclear expression of Ki-67 relative to the same tumors implan

Anti-tumor immune response varies among individuals: A gene expression profiling of mouse melanoma.

Melanoma is amongst the most aggressive malignant tumors. The purpose of this study is to detect the tumor microenvironment systematically using multi-omics analyses and to propose strategies for precision medicine. Multiple factors of tumor microenvironment contribute to the drug resistance and immune surveillance failure. Here we analyzed genome mutations and characterized the immune state of tumor microenvironments in mouse melanoma by whole exome sequencing (WES) and RNA sequencing (RNA-Seq) approaches. Somatic mutation analysis revealed 35.1% novel mutations in mouse tumors when compared …