Proliferation of tumor-related regulatory T cells in circulation dictates efficacy of chemoimmunotherapy in triple-negative breast cancer.

Purpose: PD-1/PD-L1 blockade modulates the responses of T cells including regulatory T (TREG) cells. Understanding the changes of TREG cells upon PD-1/PD-L1 blockade in cancer patients and their association with therapeutic response will provide clues regarding the mechanisms underlying resistance to treatment.

Experimental Design: Peripheral blood samples were acquired before and at 1-week post-treatment from 65 patients (triple-negative [TN], n = 35; luminal, n = 30) enrolled in KORNELIA phase 2 trial, which evaluated the efficacy of chemoimmunotherapy combining nivolumab and eribulin in HER2 negative breast cancer (BC) patients.

cGAS/STING pathway modulation in polyhexamethyleneguanidine phosphate-induced immune dysregulation and pulmonary fibrosis using human monocytic cells (THP-1) and male C57BL/6 mice.

Polyhexamethyleneguanidine phosphate (PHMG), a widely used antimicrobial agent, has been implicated in humidifier disinfectant-associated lung injuries (HDLI). PHMG exposure suppressed interferon regulatory factor 3 (IRF3) activation and interferon-β (IFN-β) expression induced by a cGAS agonist or a STING agonist in human monocytic cells (THP-1), which are known to transition to alveolar macrophages during pulmonary fibrosis development. However, the mechanisms underlying PHMG-induced pulmonary toxicity in lung remain unclear.

Real-Time Automated Solubility Screening Method Using Deep Neural Networks with Handcrafted Features.

Solubility measurements are essential in various research and industrial fields. With the automation of processes, the importance of automatic and real-time solubility measurements has increased. Although end-to-end learning methods are commonly used for classification tasks, the use of handcrafted features is still important for specific tasks with the limited labeled images of solutions used in industrial settings.

A virtual memory CD8 T cell-originated subset causes alopecia areata through innate-like cytotoxicity.

Virtual memory T (T) cells are a T cell subtype with a memory phenotype but no prior exposure to foreign antigen. Although T cells have antiviral and antibacterial functions, whether these cells can be pathogenic effectors of inflammatory disease is unclear. Here we identified a T cell-originated CD44CD49d CD8 T cell subset with features of tissue residency.

CEACAM1 Marks Highly Suppressive Intratumoral Regulatory T Cells for Targeted Depletion Therapy.

Purpose: Regulatory T cells (Tregs) exert immunosuppressive functions and hamper antitumor immune responses in the tumor microenvironment. Understanding the heterogeneity of intratumoral Tregs, and how it changes with tumor progression, will provide clues regarding novel target molecules of Treg-directed therapies.

Experimental Design: From 42 patients with renal cell carcinoma and 5 patients with ovarian cancer, immune cells from tumor and peripheral blood were isolated.

Wavelength-tunable spiral-phase-contrast imaging.

Wavelength-tunable spiral-phase-contrast (SPC) imaging was experimentally accomplished in the visible wavelengths spanning a broad bandwidth of ∼200 nm based on a single off-axis spiral phase mirror (OSPM). By the rotation of an OSPM, which was designed with an integer orbital angular momentum (OAM) of l = 1 at a wavelength of 561 nm and incidence angle of 45°, high-quality SPC imaging was obtained at different wavelengths. For the comparison with wavelength-tunable SPC imaging using an OSPM, SPC imaging using a spiral phase plate (manufactured to generate an OAM of l = 1 at 561 nm) was performed at three wavelengths (473, 561, and 660 nm), resulting in clear differences.

CD39 tissue-resident memory CD8 T cells with a clonal overlap across compartments mediate antitumor immunity in breast cancer.

Despite being a standard treatment option in breast cancer, immune checkpoint inhibitors (ICIs) are only efficacious for a subset of patients. To gain a better understanding of the antitumor immune response in breast cancer, we examined the heterogeneity of CD8 T cells in tumors, metastatic lymph nodes (mLNs), and peripheral blood from patients with early breast cancer ( = 131). Among tissue-resident memory CD8 T (T) cells, including virus- and tumor-specific CD8 T cells, CD39 expression was observed in a tumor-specific and exhausted subpopulation in both tumors and mLNs.

IFITM3 Is Upregulated Characteristically in IL-15-Mediated Bystander-Activated CD8 T Cells during Influenza Infection.

In bystander activation, pre-existing memory CD8 T cells unrelated to the infecting microbes are activated by cytokines without cognate Ags. The detailed mechanisms and unique gene signature of bystander activation remain to be elucidated. In this study, we investigated bystander activation of OT-1 memory cells in a mouse model of influenza infection.

Tumour-infiltrating bystander CD8 T cells activated by IL-15 contribute to tumour control in non-small cell lung cancer.

Background: Tumour-unrelated, virus-specific bystander CD8 T cells were recently shown to be abundant among tumour-infiltrating lymphocytes (TILs). However, their roles in tumour immunity have not been elucidated yet.

Methods: We studied the characteristics of bystander CD8 TILs from non-small cell lung cancer (NSCLC) tissues (N=66) and their activation by interleukin (IL)-15 to repurpose them for tumour immunotherapy.

Generation of wavelength-tunable optical vortices using an off-axis spiral phase mirror: publisher's note.

This publisher's note contains corrections to Opt. Lett.46, 4216 (2021)OPLEDP0146-959210.

Generation of wavelength-tunable optical vortices using an off-axis spiral phase mirror.

Wavelength-tunable optical vortices with a topological charge equal to =1 of orbital angular momentum (OAM) were experimentally realized using a single off-axis spiral phase mirror (OSPM) with lasers of various visible-light wavelengths. Using an OSPM designed for 561 nm and an incidence angle of 45°, circular doughnut-shaped =1 optical vortices were obtained at 561, 473, and 660 nm by rotating the OSPM to modify the laser incidence angle. Wavelength-tunable =1 optical vortices were obtained at the respective incidence angles of 45°, 53.

Novel anti-4-1BB×PD-L1 bispecific antibody augments anti-tumor immunity through tumor-directed T-cell activation and checkpoint blockade.

Background: Stimulation of 4-1BB with agonistic antibodies is a promising strategy for improving the therapeutic efficacy of immune checkpoint inhibitors (ICIs) or for overcoming resistance to ICIs. However, dose-dependent hepatotoxicity was observed in clinical trials with monoclonal anti-4-1BB agonistic antibodies due to the activation of 4-1BB signaling in liver resident Kupffer cells.

Methods: To avoid this on-target liver toxicity, we developed a novel bispecific antibody (4-1BB×PD-L1 bispecific antibody, termed "ABL503") uniquely designed to activate 4-1BB signaling only in the context of PD-L1, while also blocking PD-1/PD-L1 signaling.

4-1BB co-stimulation further enhances anti-PD-1-mediated reinvigoration of exhausted CD39 CD8 T cells from primary and metastatic sites of epithelial ovarian cancers.

Background: Responses to immunotherapy vary between different cancer types and sites. Here, we aimed to investigate features of exhaustion and activation in tumor-infiltrating CD8 T cells at both the primary and metastatic sites in epithelial ovarian cancer.

Methods: Tumor tissues and peripheral blood were obtained from 65 patients with ovarian cancer.

PD-1 blockade-unresponsive human tumor-infiltrating CD8 T cells are marked by loss of CD28 expression and rescued by IL-15.

Blockade of programmed death-1 (PD-1) reinvigorates exhausted CD8 T cells, resulting in tumor regression in cancer patients. Recently, reinvigoration of exhausted CD8 T cells following PD-1 blockade was shown to be CD28-dependent in mouse models. Herein, we examined the role of CD28 in anti-PD-1 antibody-induced human T cell reinvigoration using tumor-infiltrating CD8 T cells (CD8 TILs) obtained from non-small-cell lung cancer patients.