Atypical memory B cells acquire Breg phenotypes in hepatocellular carcinoma.

The functional plasticity of tumor-infiltrating B (TIL-B) cells spans from anti-tumor responses to non-canonical immune suppression. Yet, how tumor microenvironment (TME) influences TIL-B development is still underappreciated. Our current study integrated single cell transcriptomics and BCR (B cell receptor) sequencing to profile TIL-B phenotypes and clonalities in hepatocellular carcinoma (HCC).

Tumor-associated NK cells drive MDSC-mediated tumor immune tolerance through the IL-6/STAT3 axis.

Apart from their killer identity, natural killer (NK) cells have integral roles in shaping the tumor microenvironment. Through immune gene deconvolution, the present study revealed an interplay between NK cells and myeloid-derived suppressor cells (MDSCs) in nonresponders of immune checkpoint therapy. Given that the mechanisms governing the outcome of NK cell-to-myeloid cell interactions remain largely unknown, we sought to investigate the cross-talk between NK cells and suppressive myeloid cells.

Natural killer cells drive 4-1BBL positive uveal melanoma towards EMT and metastatic disease.

Background: Inflammation in the eye is often associated with aggravated ocular diseases such as uveal melanoma (UM). Poor prognosis of UM is generally associated with high potential of metastatic liver dissemination. A strong driver of metastatic dissemination is the activation of the epithelial-mesenchymal transition (EMT) regulating transcription factor ZEB1, and high expression of ZEB1 is associated with aggressiveness of UM.

Mitochondrial Dysfunction in CD4+ T Effector Memory RA+ Cells.

Human ageing is accompanied by poor responses to infection and decreased vaccine efficacy. While the causes of this can be attributed to defects in the immune system that increase with age, it is unknown whether mitochondrial dysfunction may also contribute to these phenomena. This study aims to assess mitochondrial dysfunction in CD4+ terminal effector memory T cells re-expressing CD45RA (TEMRA) cells and other CD4+ memory T cell subtypes, which are increased in number in the elderly population, with respect to how their metabolic responses to stimulation are altered compared to CD4+ naïve T cells.

Harnessing novel strategies and cell types to overcome immune tolerance during adoptive cell therapy in cancer.

Cell therapy encompasses an expanding spectrum of cell-based regimes for the treatment of human ailments, such as the use of immune cells, in particular T cells, for combating tumors and the modulation of inflammatory immune responses. In this review, we focus on cell therapy in the immuno-oncology space, which is largely driven by interests and demands from the clinics for better solutions to target various hard-to-treat cancers. We discuss recent advances in various types of cell therapies, including T cell receptor-T cells, chimeric antigen receptor (CAR)-T cells, tumor-infiltrating lymphocytes and natural killer cells.

Unravelling the role of obesity and lipids during tumor progression.

The dysregulation of the biochemical pathways in cancer promotes oncogenic transformations and metastatic potential. Recent studies have shed light on how obesity and altered lipid metabolism could be the driving force for tumor progression. Here, in this review, we focus on liver cancer and discuss how obesity and lipid-driven metabolic reprogramming affect tumor, immune, and stroma cells in the tumor microenvironment and, in turn, how alterations in these cells synergize to influence and contribute to tumor growth and dissemination.

CD25 NK cells display superior function and metabolic activity under regulatory T cell-mediated suppression.

Infusion of natural killer (NK) cells is an attractive therapeutic modality in patients with cancer. However, the activity of NK cells is regulated by several mechanisms operating within solid tumors. Regulatory T (Treg) cells suppress NK cell activity through various mechanisms including deprivation of IL-2 via the IL-2 receptor alpha (CD25).

Breast cancer patient-derived whole-tumor cell culture model for efficient drug profiling and treatment response prediction.

Breast cancer (BC) is a complex disease comprising multiple distinct subtypes with different genetic features and pathological characteristics. Although a large number of antineoplastic compounds have been approved for clinical use, patient-to-patient variability in drug response is frequently observed, highlighting the need for efficient treatment prediction for individualized therapy. Several patient-derived models have been established lately for the prediction of drug response.

Tumor MHC class I expression alters cancer-associated myelopoiesis driven by host NK cells.

Downregulation of MHC class I (MHCI) molecules on tumor cells is recognized as a resistance mechanism of cancer immunotherapy. Given that MHCI molecules are potent regulators of immune responses, we postulated that the expression of MHCI by tumor cells influences systemic immune responses. Accordingly, mice-bearing MHCI-deficient tumor cells showed reduced tumor-associated extramedullary myelopoiesis in the spleen.

Downregulation and Hypermethylation of GABPB1 Is Associated with Aggressive Thyroid Cancer Features.

Promoter mutations of the telomerase reverse transcriptase () gene occur frequently in thyroid carcinoma (TC), including papillary (PTC) and anaplastic subtypes (ATC). Given that the ETS family transcription factors GABPA and GABPB1 activate the mutant promoter and induce expression for telomerase activation, GABPB1 has been proposed as a cancer therapeutic target to inhibit telomerase. Here, we sought to determine the role of GABPB1 in TC pathogenesis.

CD11c-CD8 Spatial Cross Presentation: A Novel Approach to Link Immune Surveillance and Patient Survival in Soft Tissue Sarcoma.

Checkpoint inhibitors are slowly being introduced in the care of specific sarcoma subtypes such as undifferentiated pleomorphic sarcoma, alveolar soft part sarcoma, and angiosarcoma even though formal indication is lacking. Proper biomarkers to unravel potential immune reactivity in the tumor microenvironment are therefore expected to be highly warranted. In this study, intratumoral spatial cross presentation was investigated as a novel concept where immune cell composition in the tumor microenvironment was suggested to act as a proxy for immune surveillance.

Phosphodiesterase 4A confers resistance to PGE2-mediated suppression in CD25 /CD54 NK cells.

Inadequate persistence of tumor-infiltrating natural killer (NK) cells is associated with poor prognosis in cancer patients. The solid tumor microenvironment is characterized by the presence of immunosuppressive factors, including prostaglandin E2 (PGE2), that limit NK cell persistence. Here, we investigate if the modulation of the cytokine environment in lung cancer with IL-2 or IL-15 renders NK cells resistant to suppression by PGE2.

Thioredoxin activity confers resistance against oxidative stress in tumor-infiltrating NK cells.

To improve the clinical outcome of adoptive NK cell therapy in patients with solid tumors, NK cells need to persist within the tumor microenvironment (TME) in which the abundance of ROS could dampen antitumor immune responses. In the present study, we demonstrated that IL-15-primed NK cells acquired resistance against oxidative stress through the thioredoxin system activated by mTOR. Mechanistically, the activation of thioredoxin showed dependence on localization of thioredoxin-interacting protein.

The Multifaceted Roles of CXCL9 Within the Tumor Microenvironment.

Chemokines are soluble proteins that orchestrate cell migration in a regulated concentration gradient. During early stages of tumor development, chemokines shape the immune landscape of tumor microenvironment. CXCL9, also known as monokine induced by gamma-interferon (MIG), can be produced during inflammatory conditions by myeloid cells within the tumor microenvironment.

Immune Monitoring of Cancer Patients by Multi-color Flow Cytometry.

The irruption of immune-activating therapies to treat cancer has created a need for evaluating both the response and possible adverse events related to these novel treatments. Multicolor flow cytometry is a powerful tool that enables tumor immunologists to characterize the immune system of patients before and in response to immunotherapy. We present here a protocol for purifying human peripheral blood mononuclear cells and staining them with a set of six multicolor panels that allow for a thorough characterization of the immune system of healthy donors as well as patients that are undergoing treatments that may modify the immune system.