HAI-1 is an independent predictor of lung cancer mortality and is required for M1 macrophage polarization.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Though immune checkpoint inhibitors (ICIs) have revolutionized lung cancer therapy in recent years, there are several factors limiting the therapeutic efficacy of ICI-based immunotherapy in lung cancer. Recent evidence suggests that one such mechanism is the phenotypic shift of tumor-infiltrating macrophages away from an anti-tumor M1 phenotype and towards an anti-inflammatory and tumor-permissive M2 phenotype.

Altered Peptide Ligands Impact the Diversity of Polyfunctional Phenotypes in T Cell Receptor Gene-Modified T Cells.

The use of T cell receptor (TCR) gene-modified T cells in adoptive cell transfer has had promising clinical success, but often, simple preclinical evaluation does not necessarily accurately predict treatment efficacy or safety. Preclinical studies generally evaluate one or a limited number of type 1 cytokines to assess antigen recognition. However, recent studies have implicated other "typed" T cells in effective anti-tumor/viral immunity, and limited functional evaluations may underestimate cross-reactivity.

Critical biological parameters modulate affinity as a determinant of function in T-cell receptor gene-modified T-cells.

T-cell receptor (TCR)-pMHC affinity has been generally accepted to be the most important factor dictating antigen recognition in gene-modified T-cells. As such, there is great interest in optimizing TCR-based immunotherapies by enhancing TCR affinity to augment the therapeutic benefit of TCR gene-modified T-cells in cancer patients. However, recent clinical trials using affinity-enhanced TCRs in adoptive cell transfer (ACT) have observed unintended and serious adverse events, including death, attributed to unpredicted off-tumor or off-target cross-reactivity.

Comparative exploration of multidimensional flow cytometry software: a model approach evaluating T cell polyfunctional behavior.

Advancement in flow cytometry reagents and instrumentation has allowed for simultaneous analysis of large numbers of lineage/functional immune cell markers. Highly complex datasets generated by polychromatic flow cytometry require proper analytical software to answer investigators' questions. A problem among many investigators and flow cytometry Shared Resource Laboratories (SRLs), including our own, is a lack of access to a flow cytometry-knowledgeable bioinformatics team, making it difficult to learn and choose appropriate analysis tool(s).

Hepatitis C virus-cross-reactive TCR gene-modified T cells: a model for immunotherapy against diseases with genomic instability.

A major obstacle hindering the development of effective immunity against viral infections, their associated disease, and certain cancers is their inherent genomic instability. Accumulation of mutations can alter processing and presentation of antigens recognized by antibodies and T cells that can lead to immune escape variants. Use of an agent that can intrinsically combat rapidly mutating viral or cancer-associated antigens would be quite advantageous in developing effective immunity against such disease.

TCR gene-modified T cells can efficiently treat established hepatitis C-associated hepatocellular carcinoma tumors.

The success in recent clinical trials using T cell receptor (TCR)-genetically engineered T cells to treat melanoma has encouraged the use of this approach toward other malignancies and viral infections. Although hepatitis C virus (HCV) infection is being treated with a new set of successful direct anti-viral agents, potential for virologic breakthrough or relapse by immune escape variants remains. Additionally, many HCV+ patients have HCV-associated disease, including hepatocellular carcinoma (HCC), which does not respond to these novel drugs.

Characterization of uptake and internalization of exosomes by bladder cancer cells.

Bladder tumors represent a special therapeutic challenge as they have a high recurrence rate requiring repeated interventions and may progress to invasive or metastatic disease. Exosomes carry proteins implicated in bladder cancer progression and have been implicated in bladder cancer cell survival. Here, we characterized exosome uptake and internalization by human bladder cancer cells using Amnis ImageStreamX, an image cytometer.