IGFBP2 is highly expressed in EC tissues and correlated with poor prognosis. IGFBP2/PKM2/HIF-1α positive feedback loop promotes glycolytic metabolism and tumorigenesis.
CAFs have been proposed as key tumor-promoting players and promising therapeutic targets for cancer. This review summarizes the origins and diversity of CAFs, their role in cancer, and current therapeutic strategies aimed at targeting CAFs, including ongoing clinical evaluations.
Melanoma-associated antigen (MAGE)-A4, a cancer testis antigen, presents a promising target for immunotherapies in refractory solid tumors, including breast cancer (BC). However, the lack of highly specific Abs against MAGE-A4 is a major challenge for the development of MAGE-A4-targeted immunotherapies. In this study, we determined that E701U Ab has reliable specificity for MAGE-A4 expression, and MAGE-A4-positive BC displays an unfavorable prognosis and could represent promising targets for MAGE-A4-specific immunotherapy.
Near-infrared photoimmunotherapy (NIR-PIT) is a novel antitumor therapy that selectively kills cancer cells by NIR light-triggered transformation of IRDye700DX within Ab–photoabsorber conjugates (APCs). NIR-PIT effectively induces immunogenic cell death, immune cell migration between the tumor and tumor-draining lymph node, and expansion of multiclonal tumor-infiltrating CD8+ T cells. Crucially, cytotoxic effects of NIR-PIT exert only cancer cells, sparing immune cells such as antigen-presenting cells and T cells, key players in boosting antitumor host immunity. By modifying the Ab used in APC synthesis, NIR-PIT can target and deplete noncancerous immunosuppressive cells including regulatory T cells, myeloid-derived suppressor cells, and cancer-associated fibroblasts, in the tumor microenvironment. Immunosuppressive cell-targeted NIR-PIT strongly potentiate antitumor host immunity, including the induction of abscopal effects and the development of immune memory. Furthermore, antitumor immune responses and therapeutic efficacy are synergistically enhanced when combining NIR-PIT with other immune-activating treatments, such as interleukin-15 and immune checkpoint inhibitors. This evidence identifies NIR-PIT as a valuable tool in the evolving landscape of cancer immunotherapy. This review presents the role of NIR-PIT in activating antitumor host immunity.
Spatial immune heterogeneity in the tumor microenvironment and its drivers in a mouse model of tumors induced by human papillomaviruses were investigated following immunotherapy. Gene expression was determined by RNA sequencing and mutations by whole exome sequencing in different tumor areas. This study describes the intratumoral immune heterogeneity, that could lead to tumor immune escape, and suggests the potential mechanisms involved.
In the present study, we showed that the combination of glycoprotein nonmetastatic melanoma protein B (GPNMB) and fibroblast growth factor receptor 1 (FGFR1) would be a novel poor prognostic indicator in patients with triple-negative breast cancer (TNBC.) Furthermore, we found GPNMB as a novel binding partner of FGFR1, and they are important for the tumorigenic ability of TNBC cells through the regulation of AKT phosphorylation. Therefore, this association could be the potential therapeutic target to control TNBC.
The pan-immune-inflammation value (PIV), reflecting immune and inflammatory status, correlates with disease-free survival (DFS) and cancer-specific survival (CSS) in rectal cancer patients. PIV-low patients exhibit immune activation and sensitivity to immunotherapy, while PIV-high is associated with tumor progression pathways.
E3 ubiquitin ligase TRIM47 overexpresses in hypopharyngeal cancer and is related to poor prognosis. TRIM47 regulates vimentin which is associated with metastasis with K63-linked ubiquitination in hypopharyngeal and laryngeal cancers.
By analyzing the cancer stem-like phenotype, multiomics features, and molecular mechanisms of cell cluster formation and collective invasion of micropapillary carcinoma, and integrating the vascular and immune microenvironment of micropapillary carcinoma, it is suggested that micropapillary carcinoma has the potential to become a solid tumor model for studying the invasion and metastasis of cancer stem cell clusters.
Signaling lymphocytic activation molecule family 7 (SLAMF7), an important therapeutic target of myeloma cells, is highly expressed in osteoclasts. Ex vivo-expanded human Vγ9Vδ2 T cells are able to efficaciously exert antibody-dependent cellular cytotoxicity (ADCC) with the anti-SLAMF7 monoclonal antibody elotuzumab for SLAMF7-expressing myeloma cells and osteoclasts even in their coculture settings. Vγ9Vδ2 T cells can be utilized as effectors for immunotherapy besides their direct antitumor activity.
Targeting CLK2 shows antitumor effects on multiple myeloma. Its mechanism is partially through inhibiting serine/arginine-rich splicing factor phosphorylation, and inducing nonsense-mediated mRNA decay of RAE1 by exon 9 skipping.
This study demonstrates a molecular mechanism by which normal cells sense and respond to oncogenic stress driven by aberrant ERK activity to prevent tumorigenesis, and how its dysregulation occurs in cancer. In this process, GADD45β, an activator of the MTK1 MAPKKK, is selectively upregulated by oncogenic ERK signaling, leading to the activation of MTK1-p38/JNK signaling and the induction of apoptosis in normal cells. However, this tumor-suppressive signaling pathway is frequently inactivated in cancer, thereby promoting tumor progression.
The combination of the chemopreventive agents bexarotene (Bex) and carvedilol (Carv) suppresses the zymogen granule protein 16B (ZG16B, PAUF) through a newly discovered interaction of ARID1A with a proximal enhancer. ZG16B stimulates mesenchymal characteristics and promotes proliferation, motility and a shift in matrix properties toward increased density and cell-matrix interactions. ZG16B is a druggable pro-tumorigenic target in breast cell transformation and suggests a key role of the matrisome network in rexinoid-dependent antitumor activity.
This nationwide case-control study in Japan aimed to estimate the effectiveness of the HPV vaccine against CIN3+ in Japanese women and demonstrated that HPV vaccination reduces the risk of CIN3+ by 86%.
Epstein–Barr virus (EBV)-associated and microsatellite instability (MSI)-high tumors evade antitumor immunity mainly by expressing programmed death-ligand 1. However, little is known about the tumor immune microenvironment of non-EBV/non-MSI-high tumors. Here, we show that the FOXP3+/CD8+ ratio differs by histology, with a high ratio at the invasive margin associated with an unfavorable prognosis in the diffuse histological subtype of non-EBV/non-MSI-high esophagogastric junction adenocarcinoma. This is particularly evident in RUNX3−methylated tumors, which might be linked to CCL28 production.
SET as a potential target for microsatellite stability colorectal cancer. SET promotes mismatch repair protein expression in a c-Myc-dependent manner. SET impairs FBXW7-mediated c-Myc ubiquitination and degradation in MSS CRC.
This article provides a comprehensive review of recent research advancements in the field of tumor immunology, focusing particularly on a unique subset of CX3CR1+CD8+ T cells and their distinct advantages. These cells show immense potential in tumor immunotherapy, especially within the realm of cellular immunotherapy, due to their ability to migrate toward tumors, exert cytotoxic effects, selectively recognize tumor cells, and exhibit minimal expression of co-inhibitory molecules. Concurrently, the effectiveness of chimeric antigen receptor T (CAR-T) cells expressing high levels of CX3CR1 in the clinical management of solid tumors requires further validation through future phase I and II clinical trials. Indeed, as research advances, these pioneering approaches are poised to offer new avenues of hope for countless cancer patients.
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