Pancreatic ductal adenocarcinoma (PDAC) is characterized by remarkable desmoplasia with infiltration of distinct cellular components. Cancer‐associated fibroblasts (CAFs) has been shown to be among the most prominent cells and played a significant role in shaping the tumor microenvironment by interacting with other type of cells. Here, we aimed to investigate the effect of CAFs in modulating phenotype of tumor‐associated macrophages (TAM). Under treatment of CAFs conditioned medium (CM) or direct co‐culture with CAFs, monocytes exhibited enhanced expression of CD206 and CD163 compared with control group (P < 0.01). The induction of M2 polarization was mediated by increased reactive oxygen species (ROS) production in monocytes as ROS elimination abolished the effect of CAFs (P < 0.05). The supernatant analysis showed that pancreatic CAFs produced increased macrophage colony‐stimulating factor (M‐CSF). Upon treatment of M‐CSF neutralizing antibody, the ROS generation and M2 polarization of CAFs CM‐stimulated monocytes were significantly inhibited (P < 0.05). In addition, the CAFs‐induced M2 macrophages significantly enhanced pancreatic tumor cell growth, migration, and invasion. Collectively, our data revealed that pancreatic CAFs were able to induce a tumor‐promoting TAM phenotype partly through secreted M‐CSF and enhanced ROS production in monocytes, indicating possible treatment strategies by targeting stromal cell interaction within PDAC microenvironment.

Our findings for the first time demonstrated up-regulated B7-H1 expression in human pancreatic carcinoma tissues, which might play a role in tumor progression and invasiveness. This expression seemed to be related to the ability of B7-H1 to promoting IL-10 secretion.

TLR4 (Toll-like receptor 4) and B7-H1, which were known to be restricted to immune cells in the past, were found to be aberrantly expressed in a majority of tumor cells, facilitating tumor evasion from immune surveillance. Our study demonstrated that activation of TLR4 signaling in bladder cancer cells up-regulated B7-H1 expression. Furthermore, this regulation was significantly attenuated by ERK or JNK inhibitor. Our results elucidated the molecule mechanism of regulation of B7-H1 expression through TLR4 signaling and may suggest new strategies of down-regulating the cancer-associated B7-H1 expression for bladder cancer treatment.

Cancer photodynamic therapy (PDT) represents an attractive local treatment in combination with immunotherapy. Successful cancer PDT relies on image guidance to ensure the treatment accuracy. However, existing nanotechnology for co-delivery of photosensitizers and image contrast agents slows the clearance of PDT agents from the body and causes a disparity between the release profiles of the imaging and PDT agents. We have found that the photosensitizer Chlorin e6 (Ce6) is inherently bound to immunoglobulin G (IgG) in a nanomolarity range of affinity. Ce6 and IgG self-assemble to form the nanocomplexes termed Chloringlobulin (Chlorin e6 + immunoglobulin G). Chloringlobulin enhances the Ce6 concentration in the tumor without changing its elimination half-life in blood. Utilizing the immune checkpoint inhibitor antiprogrammed death ligand 1 (PD-L1) (αPD-L1) to prepare αPD-L1 Chloringlobulin, we have demonstrated a combination of Ce6-based red-light fluorescence image-guided surgery, stereotactic PDT, and PD-L1 blockade therapy of mice bearing orthotopic glioma. In mice bearing an orthotopic colon cancer model, we have prepared another Chloringlobulin that allows intraoperative fluorescence image-guided PDT in combination with PD-L1 and cytotoxic T lymphocyte antigen 4 (CTLA-4) dual checkpoint blockade therapy. The Chloringlobulin technology shows great potential for clinical translation of combinatorial intraoperative fluorescence image-guided PDT and checkpoint blockade therapy.

Color vision deficiencies appear to influence the development of myopia. The observed lower incidence of myopia in people with CVD may be linked to the reduced functionality of the L/M chromatic mechanism.