Systemic chemokine-modulatory regimen combined with neoadjuvant chemotherapy in patients with triple-negative breast cancer.

Background: Higher cytotoxic T lymphocyte (CTL) numbers in the tumor microenvironment (TME) predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and positive long-term outcomes in triple-negative breast cancer (TNBC). pCR to NAC is achieved only in 30-40% of patients. The combination of NAC with pembrolizumab increases the pCR rate but at the cost of immune-related adverse events (irAEs).

Dendritic Cell Plasticity, Radiation, and Newton's Third Law.

Regulatory T cells protect damaged tissues but can undermine the effects of cancer treatments, including radiotherapy (RTx). Intratumoral immunostimulatory dendritic cells (type 1 conventional dendritic cells) respond to RTx with the production of regulatory T cell-attracting MDC/CCL22, undermining RTx effects. That effect can be reversed by EGFR-targeted IFNα, highlighting cDC1 plasticity and relevance as therapeutic targets.

Targeting the tumor microenvironment to improve clinical outcomes in triple negative breast cancer patients and bridge the current disparity gap.

Triple negative breast cancer (TNBC) is a heterogenous disease that disproportionately affects Black women. TNBC outcomes among Black women are dismal secondary to multiple factors, such as poor healthcare accessibility resulting in delays in diagnosis, and aggressive disease biology in addition to a pro-tumor immune microenvironment (TME). Black women with breast cancer exhibit elevated levels of serum pro-inflammatory cytokines, and a pro-tumorigenic TME with higher immunosuppressive regulatory T cells (Tregs), M2 macrophages and exhausted CD8 T cells.

Therapeutic Anti-Tumor Efficacy of DC-Based Vaccines Targeting TME-Associated Antigens Is Improved When Combined with a Chemokine-Modulating Regimen and/or Anti-PD-L1.

We previously reported that dendritic cell (DC)-based vaccines targeting antigens expressed by tumor-associated vascular endothelial cells (VECs) and pericytes effectively control tumor growth in translational mouse tumor models. In the current report, we examined whether the therapeutic benefits of such tumor blood vessel antigen (TBVA)-targeted vaccines could be improved by the cotargeting of tumor antigens in the s.c.

NK Receptor Signaling Lowers TCR Activation Threshold, Enhancing Selective Recognition of Cancer Cells by TAA-Specific CTLs.

Cytotoxic CD8+ T lymphocyte (CTL) recognition of non-mutated tumor-associated antigens (TAA), present on cancer cells and also in healthy tissues, is an important element of cancer immunity, but the mechanism of its selectivity for cancer cells and opportunities for its enhancement remain elusive. In this study, we found that CTL expression of the NK receptors (NKR) DNAM1 and NKG2D was associated with the effector status of CD8+ tumor-infiltrating lymphocytes and long-term survival of patients with melanoma. Using MART1 and NY-ESO-1 as model TAAs, we demonstrated that DNAM1 and NKG2D regulate T-cell receptor (TCR) functional avidity and set the threshold for TCR activation of human TAA-specific CTLs.