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BackgroundOnco-immunogenic molecule CD155 is overexpressed in various tumor microenvironments (TME) including in colorectal cancer (CRC). Tumor-associated macrophages (TAMs) are the most abundant immune cells in CRC TME and play a vital role in CRC progression and metastasis. Most studies have focused on investigating the role of CRC cell-specific CD155 on CRC progression, while the contribution of TAMs-specific CD155 is still unknown. Here, we sought to investigate the expression pattern of CD155 in CRC TAMs and its role in tumor immunity and progression.MethodsCD155 expression patterns in CRC TAMs and macrophages in paratumor or adjacent normal tissue were analyzed in 50 patients with CRC using flow cytometry and in 141 patients with CRC using immunohistochemistry. The correlation of CD155 expression level in TAMs with M1 and M2 phenotypic transition was analyzed. The role of macrophage-specific CD155 in CRC progression and tumor immune response was investigated in vitro and in vivo. We further analyzed the effect of CRC cells on the regulation of CD155 expression in macrophages.ResultsCRC TAMs from clinical samples showed robustly higher expression of CD155 than macrophages from paratumor and adjacent normal tissues. The CD155 expression level was higher in TAMs of CRC at III/IV stages compared with the I/II stages and was negatively associated with the survival of patients with CRC. CD155+ TAMs showed an M2 phenotype and higher expression of interleukin (IL)-10 and transforming growth factor (TGF)-β. CD155+ macrophages promoted CRC cell migration, invasion, and tumor growth supporting the findings from the clinical tissue analysis. This effect was mainly regulated by TGF-β-induced STAT3 activation-mediated release of matrix metalloproteinases (MMP)2 and MMP9 in CRC cells. CD155–⁄– bone marrow transplantation in wild-type mice, as well as CD155– macrophages treatment, promoted the antitumor immune response in the mice ectopic CRC model. Additionally, CRC cells released IL-4 to trigger CD155 expression in macrophages indicating the regulatory role of CRC cells in the development of CD155+ TAMs.ConclusionsThese findings indicated that CD155+ TAMs are responsible for the M2-phenotype transition, immunosuppression, and tumor progression in CRC. The specific localization of CD155+ TAMs in CRC tissue could turn into a potential therapeutic target for CRC treatment.

Neurogenic erectile dysfunction (nED) is one of the most common and intractable postoperative complications of rectal and prostate cancer surgery and sometimes accompanies patients lifelong. The transplantation of stem cells has been proved a promising way for treatment. However, the therapeutic efficacy is severely impaired by excessive cell loss and death and poor accumulation in the injury site along with the traditional implantation strategy. Herein, an EPO-loaded multifunctional hydrogel was designed. The hydrogels' adhesive property and mechanical strength were enhanced by adding catechol-catechol adducts, thus significantly improving adipose-derived stem cells (ADSC) retention and rescuing cell loss in the injury site. Meanwhile, the sustained release of EPO effectively ameliorated the viability and paracrine activity of ADSC, leading to enhanced migration of Schwann cells and differentiation of PC12 cells in vivo. On a bilateral cavernous nerve injury rat model, the present stem cell-EPO-hydrogel implanted strategy could significantly alleviate erectile dysfunction. The higher expression of Tuj1 and lower expression of GFAP in the major pelvic ganglia (MPG) indicated the acceleration of neural differentiation while the suppressing development of astrocytes. Also, the combined therapy restored the expression levels of eNOs, nNOs, and α-SMA in penile tissues, suggesting the rehabilitation of the penis. Further analysis of Masson trichrome staining and apoptosis evaluation of the corpus cavernosum showed the preservation of vascular endothelium content and the prevention of penile fibrosis after denervation. Overall, we believe that this combined strategy presents a promising way not only for restoring neurogenic erectile function but also for the clinical translation of stem cell therapy.

Jun Shao,1,* Rongpu Liang,1,* Dongbing Ding,1,* Xiaoming Zheng,1 Xudong Zhu,1 Shengxue Hu,2 Hongbo Wei,1 Bo Wei1 1Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, People’s Republic of China; 2College of Biological Science and Engineering, Fuzhou University, Fujian, 350108, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongbo Wei; Bo WeiDepartment of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, People’s Republic of ChinaTel +86-20-85252228Email weihb@mail.sysu.edu.cn; weibo3@mail.sysu.edu.cnBackground: Surgery is considered to be a potentially curative approach for gastric cancer. However, most cases are diagnosed at a very advanced stage for the lack of typical symptoms in the initial stage, which makes it difficult to completely surgical resect of tumors. Early diagnosis and precise personalized intervention are urgent issues to be solved for improving the prognosis of gastric cancer. Herein, we developed an RGD-modified ROS-responsive multifunctional nanosystem for near-infrared (NIR) imaging and photothermal therapy (PTT) against gastric cancer.Methods: Firstly, the amphiphilic polymer was synthesized by bromination reaction and nucleophilic substitution reaction of carboxymethyl chitosan (CMCh) and 4-hydroxymethyl-pinacol phenylborate (BAPE). Then, it was used to encapsulate indocyanine green (ICG) and modified with RGD to form a smart multifunctional nanoparticle targeted to gastric cancer (CMCh-BAPE-RGD@ICG). The characteristics were determined, and the targeting capacity and biosafety were evaluated both in vitro and in vivo. Furthermore, CMCh-BAPE-RGD@ICG mediated photothermal therapy (PTT) effect was studied using gastric cancer cells (SGC7901) and SGC7901 tumor model.Results: The nanoparticle exhibited suitable size (≈ 120 nm), improved aqueous stability, ROS-responsive drug release, excellent photothermal conversion efficiency, enhanced cellular uptake, and targeting capacity to tumors. Remarkably, in vivo studies suggested that CMCh-BAPE-RGD@ICG could accurately illustrate the location and margin of the SGC7901 tumor through NIR imaging in comparison with non-targeted nanoparticles. Moreover, the antitumor activity of CMCh-BAPE-RGD@ICG-mediated PTT could effectively suppress tumor growth by inducing necrosis and apoptosis in cancer cells. Additionally, CMCh-BAPE-RGD@ICG demonstrated excellent biosafety both in vitro and in vivo.Conclusion: Overall, our study provides a biocompatible theranostic nanoparticle with enhanced tumor-targeting ability and accumulation to realize NIR image-guided PTT in gastric cancer.Keywords: gastric cancer, nanoparticle, indocyanine green, near-infrared imaging, photothermal therapy

TIGIT is a lymphocyte surface receptor, which is mainly expressed on the surface of CD8+T cells. The role of TIGIT in colorectal cancer and its expression pattern in colorectal cancer infiltrating lymphocytes are still controversial. This study aimed at identifying the function of TIGIT in colorectal cancer. Patients with colorectal cancer showed significantly higher TIGIT+CD8+T cell infiltration in tumor tissues, metastases compared with paired PBMC and normal tissues through flow cytometry. TIGIT+CD8+T cells showed an exhausted phenotype and expressed low levels of killer cytokines IFN-γ, IL-2, TNF-α. In addition, more inhibitory receptors such as PD-1, LAG-3, and TIM-3 were expressed on the surface of TIGIT+CD8+T cells. TGF-β1 could promote the expression of TIGIT and inhibit CD8+T cell function in vitro. Moreover, the accumulation of TIGIT+T cells in tumors was associated with advanced disease, predicted early recurrence, and reduced survival rates in colorectal cancer patients. Our results indicate that TIGIT can be a biological marker for the prognosis of colorectal cancer, and TIGIT can be used as a potential target for treatment.

Shao J, Liang R, Ding D, Zheng X, et al.Int J Nanomedicine. 2021;16:2897–2915. The authors have advised due to an error at the time offigure assembly, Figure 8F on page 2911 is incorrect. Thecorrect Figure 8 is shown below. The authors apologize for this error and advise it does notaffect the results of the paper. Read the original article

An ideal tumor treatment is supposed to eliminate the primary tumor and simultaneously trigger the host antitumor immune responses to prevent tumor recurrence and metastasis. Herein, a liposome encapsulating phosphoinositide 3‐kinase gamma (PI3Kγ) inhibitor IPI‐549 and photosensitizer chlorin e6 (Ce6), denoted by LIC, is prepared for colon cancer treatment. LIC internalized into CT26 cells generates reactive oxygen species (ROS) under laser irradiation to cause immunogenic tumor cell death, during which immunostimulatory signals such as calreticulin are released to further induce T lymphocyte‐mediated tumor cell killing. Meanwhile, IPI‐549 transported by liposome can inhibit PI3Kγ in the myeloid‐derived suppressive cells (MDSCs), resulting in downregulation of arginase 1 (Arg‐1) and ROS to promote MDSCs apoptosis and reduce their immunosuppressive activity to CD8+ T cells. LIC‐mediated immunogenic photodynamic therapy synergizes with MDSCs‐targeting immunotherapy, which significantly inhibits tumor growth via facilitating the dendritic cell maturation and tumor infiltration of CD8+ T cells while decreasing the tumor infiltration of immunosuppressive regulatory T cells, MDSCs, and M2‐like tumor‐associated macrophages. Moreover, the synergistic therapy increases the number of effector memory T cells (TEM) in spleen, which suggests a favorable immune memory to prevent tumor recurrence and metastasis. The Ce6 and IPI‐549‐coloaded multifunctional nanodrug demonstrates high efficacy in colon cancer treatment., A liposome encapsulating phosphoinositide 3‐kinase gamma inhibitor IPI‐549 and photosensitizer chlorin e6 (Ce6) mediates immunogenic photodynamic therapy synergizing with myeloid‐derived suppressive cells (MDSCs)‐targeting immunotherapy, which significantly inhibits colon cancer growth via facilitating the dendritic cells maturation and tumor infiltration of CD8+ T cells while decreasing the tumor infiltration of immunosuppressive regulatory T cells, MDSCs, and M2‐like tumor‐associated macrophages.

TIGIT is a lymphocyte surface receptor, which is mainly expressed on the surface of CD8

Early diagnosis and complete resection of the tumor is an important way to improve the quality of life of patients with gastric cancer. In recent years, near-infrared (NIR) materials show great potential in fluorescence-based imaging of the tumors. To realize a satisfying intraoperative fluorescence tumor imaging, there are two pre-requirements. One is to obtain a stable agent with a relatively longer circulation time. The second is to make it good biocompatible and specific targeting to the tumor. Here, we developed an RGD-modified Distearyl acylphosphatidyl ethanolamine-polyethylene glycol micelle (DSPE-PEG-RGD) to encapsulate indocyanine green (ICG) for targeting fluorescence imaging of gastric cancer, aimed at realizing tumor-targeted accumulation and NIR imaging. 1H NMR spectroscopy confirmed its molecular structure. The characteristics and stability results indicated that the DSPE-PEG-RGD@ICG had a relatively uniform size of

Metastasis, a life-threatening complication of cancer, leads to the majority of cases of cancer-associated mortality. Unfortunately, the underlying molecular and cellular mechanisms of cancer metastasis remain to be fully elucidated. C-type lectins are a large group of proteins, which share structurally homologous carbohydrate-recognition domains (CRDs) and possess diverse physiological functions, including inflammation and antimicrobial immunity. Accumulating evidence has demonstrated the contribution of C-type lectins in different steps of the metastatic spread of cancer. Notably, a substantial proportion of C-type lectins, including selectins, mannose receptor (MR) and liver and lymph node sinusoidal endothelial cell C-type lectin, are important molecular targets for the formation of metastases in vitro and in vivo. The present review summarizes what has been found regarding C-type lectins in the lymphatic and hematogenous metastasis of cancer. An improved understanding the role of C-type lectins in cancer metastasis provides a comprehensive perspective for further clarifying the molecular mechanisms of cancer metastasis and supports the development of novel C-type lectins-based therapies the for prevention of metastasis in certain types of cancer.

Duodenal mucinous adenocarcinoma (DMA) is a malignancy with a rather low morbidity. However, its incidence in China has not been clearly determined. We herein report a case of a 70-year-old female patient who presented with ileus, obstructive jaundice and massive ascites simultaneously. Gastroendoscopy revealed copious amounts of colloidal mucin in the gastric cavity. The neoplasm was not visualized on computed tomography or magnetic resonance imaging, and an exploratory laparotomy was performed to investigate the abdomen. During the operation, the anterior wall of the gastric antrum was incised to explore the first and second portions of the duodenum, as well as the gastric lumen, and a neoplasm sized ~2.0 cm was identified at the antimesenteric border of the duodenal bulb after clearing the colloidal mucin content of the stomach and duodenum. Gastrojejunostomy rather than radical resection was performed due to the poor condition of the patient. The postoperative histopathological examination of the colloidal substance removed from the duodenal cavity revealed mucinous adenocarcinoma. On immunohistochemical analysis, the tissue stained positive for pan-cytokeratin, cytokeratin 19, CDX-2, carcinoembryonic antigen and Ki-67 (8%), and negative for excision repair-1. The general condition of the patient postoperatively was poor; thus, adjuvant chemotherapy was not administered and the patient finally succumbed to the disease 42 days after surgery.

Soluble mannose receptor (sMR) and soluble haemoglobin scavenger receptor (sCD163) are macrophage activation markers which have previously been demonstrated to be increased in patients with inflammation, auto-immunity and malignancies. To investigate the clinical diagnostic and prognostic significance of preoperative serum sMR and sCD163, the present study investigated 143 gastric cancer (GC) patients, 66 subjects with benign gastric disease and 59 healthy controls, using an ELISA assay. Preoperative serum levels of sMR and sCD163 ranged from 0.165 to 0.885 µg/ml (median=0.374 µg/ml) and from 0.291 to 1.760 µg/ml (median=0.628 µg/ml) in GC patients, respectively. The expression levels of sMR and sCD163 were elevated compared with all controls (P

Primary gastrointestinal non-Hodgkin lymphoma (PGI NHL) is one of the most common types of extranodal lymphoma, accounting for ~30–50% of all extranodal lymphomas. The aim of the present study was to investigate the clinical characteristics, diagnosis, treatment and prognosis of patients with PGI NHL. A total of 46 patients with PGI NHL (mean age, 50 years) were enrolled in this study, with a male:female ratio of 1.3:1. The most common site of PGI NHL was the stomach (52.2%), followed by the colon (34.8%) and small intestine (8.7%). The most common symptoms of PGI NHL included abdominal pain or discomfort (91.3%), loss of appetite (65.2%) and weight loss (56.5%) and the most common pathological subtype of PGI NHL was diffuse large B-cell lymphoma (DLBCL) (78.3%). Lesions were identified in 95.7% of PGI NHL patients under preoperative endoscopic examination, whereas the diagnosis rate was only 21.7% during preoperative endoscopic biopsy. All 46 patients underwent surgical treatment and 36 also received postoperative chemotherapy or radiotherapy. The follow-up time was 6–70 months in 37 PGI NHL patients, with 1-, 3- and 5-year survival rates of 81.1, 62.16 and 50.0%, respectively. The 5-year survival rate differed significantly according to clinical stage (P=0.002) and tumor size (P=0.0017) among patients with PGI NHL. However, there was no statistically significant difference in the 5-year survival rate between patients who received surgery alone and those who received surgery plus postoperative chemotherapy or radiotherapy (P=0.1371). Furthermore, there were no statistically significant differences in gender (P=0.127), clinical stage (P=0.828), histological subtype (P=1.000) and surgical modality (P=0.509) between patients with primary gastric non-Hodgkin lymphoma (PG NHL) and those with primary intestinal non-Hodgkin lymphoma (PI NHL). In conclusion, PGI NHLs are a heterogeneous group of diseases, whereas clinical stage and tumor size were identified as adverse prognostic factors of PGI NHL. Further studies, including a larger number of patients treated with surgery alone, are required in order to elucidate the precise role of surgery combined with postoperative chemotherapy or radiotherapy in the prognosis of PGI NHL.

BackgroundColon cancer has always been diagnosed at a late stage, which is associated with poor prognosis. The currently used serum tumor markers CEA and CA19-9 display low sensitivity and specificity and may not have diagnostic value in early stage colon cancer. Thus, there is an urgent need to identify novel serum biomarkers for use in the early detection of colon cancer.MethodsIn this study, the expression of DC-SIGN and DC-SIGNR in serum was detected by enzyme-linked immunosorbent assay (ELISA). DC-SIGN and DC-SIGNR expression was detected in cancer tissues by immunohistochemistry (IHC).ResultsThe level of sDC-SIGN was lower in patients than in the healthy controls, while the level of sDC-SIGNR in patients was higher than in the healthy controls. Both sDC-SIGN and sDC-SIGNR had diagnostic significances for cancer patients, and the combined diagnosis of these two markers was higher than both of them alone. Furthermore, there were significant differences between both sDC-SIGN and sDC-SIGNR in stage I/II patients and the healthy controls. Moreover, high sDC-SIGN level was accompanied with the long survival time. Additionally, DC-SIGNR was negative in the cancer foci and matched normal colon tissues but was weakly positive between the cancer foci. DC-SIGN staining was faint in matched normal colon tissues, strong in the tumor stroma and the invasive margin of colon cancer tissues, and negatively correlated with the sDC-SIGN level in serum from the same patient. Interestingly, the percent survival of patients with a DC-SIGN mean density of>0.001219 (the upper 95% confidence interval of matched normal colon tissues) was higher than for all other patients.ConclusionDC-SIGN and DC-SIGNR are blood-based molecular markers that can potentially be used for the diagnosis of early stage patients. Moreover, expression of DC-SIGN in serum and cancer tissues may affect the survival time for colon cancer patients.