Interleukin‑17 (IL‑17), an inflammatory cytokine primarily secreted by T helper 17 cells, serves a crucial role in numerous inflammatory diseases and malignancies via its receptor, IL‑17R. In addition to stimulating inflammatory responses, IL‑17 exhibits dual functions in tumors, exerting both pro‑ and antitumor effects. Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy and accounts for >90% of pancreatic cancer cases. PDAC is characterized by a prominent stromal microenvironment with significant heterogeneity, which contributes to treatment resistance. IL‑17/IL‑17R signaling has a notable effect on tumorigenesis, the tumor microenvironment and treatment efficacy in various cancer types, including PDAC. However, the specific mechanisms of IL‑17/IL‑17R signaling in pancreatic cancer remain uncertain. This review presents a brief overview of the current knowledge and recent advances in the role and functional mechanisms of IL‑17/IL‑17R signaling in pancreatic cancer. Furthermore, the potential of IL‑17‑targeted therapeutic strategies for PDAC treatment is also discussed.

OBJECTIVE: Coloanal anastomosis with loop diverting ileostomy (CAA) is an option for low anterior resection of the rectum, and Turnbull-Cutait coloanal anastomosis (TCA) regained popularity in the effort to offer patients a reconstructive option. In this context, we aimed to compare both techniques.
METHODS: PubMed, Cochrane, and Scopus were searched for studies published until January 2024. Odds ratios (RRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. Statistical significance was defined as p < 0.05. Heterogeneity was assessed using the Cochran Q test and I2 statistics, with p-values inferior to 0.10 and I2 >25% considered significant. Statistical analysis was conducted in RStudio version 4.1.2 (R Foundation for Statistical Computing). Registered number CRD42024509963.
RESULTS: One randomized controlled trial and nine observational studies were included, comprising 1,743 patients, of whom 899 (51.5%) were submitted to TCA and 844 (48.5%) to CAA. Most patients had rectal cancer (52.2%), followed by megacolon secondary to Chagas disease (32.5%). TCA was associated with increased colon ischemia (OR 3.54; 95% CI 1.13 to 11.14; p < 0.031; I2 = 0%). There were no differences in postoperative complications classified as Clavien-Dindo ≥ IIIb, anastomotic leak, pelvic abscess, intestinal obstruction, bleeding, permanent stoma, or anastomotic stricture. In subgroup analysis of patients with cancer, TCA was associated with a reduction in anastomotic leak (OR 0.55; 95% CI 0.31 to 0.97 p = 0.04; I2 = 34%).
CONCLUSIONS: TCA was associated with a decrease in anastomotic leak rate in subgroups analysis of patients with cancer.

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is an immunoglobulin superfamily protein primarily expressed on epithelial surfaces and myeloid cells. It plays a significant role in cancer progression by inhibiting apoptosis, promoting drug resistance, and facilitating cancer cell invasion and metastasis. Overexpression of CEACAM6 has been observed in various cancers, including lung, breast, colorectal, and hepatocellular cancers, and is associated with poorer overall survival and disease-free survival. Its differential expression on tumor cell surfaces makes it a promising cancer marker. This review aims to provide a comprehensive summary of CEACAM6\'s role in different cancer types, its involvement in signaling pathways, and recent advancements in CEACAM6-targeted treatments.

To report the first and largest systematic review and meta-analysis of radomised controlled trials (RCTs) to compare the efficacy and safety of transanal endoscopic microsurgery (TEM) and total mesorectal excision (TME) for rectal cancer for perioperative and oncological outcomes. Methods: We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until December 2022 for RCTs which evaluated the efficacy and/or safety between TEM and TME for rectal cancer. Outcomes included operative time, blood loss, transfusion rates, hospital stay, complication rates, recurrence rates, and mortality. Results: A total of 5 RCTs involving 545 patients (272 TEM versus 273 TME) were included for the meta-analysis. There were no significant differences between the two groups for age, gender, and distance from lower border of tumor to anal verge. Meta-analysis found that the TEM group was significantly favorable than the TME group for blood loss (WMD: 172.01; 95 % CI: 212.78, -131.24; P < 0.00001), hospital stay (WMD: 2.58; 95 % CI: 3.01, -2.16; P < 0.00001), operative time (WMD: 81.86; 95 % CI: 87.51, -76.21; P < 0.00001) and transfusion rates (RR: 0.05; 95 % CI: 0.01, 0.38; P = 0.004). The complication rates (RR: 0.60; 95 % CI: 0.32, 1.11; P = 0.10), recurrence rates (RR: 1.10; 95 % CI: 0.66, 1.83; P = 0.72), and mortality (RR: 1.23; 95 % CI: 0.67, 2.26; P = 0.51) were similar in the two groups. Conclusions: TEM was an effective and safe approach with advantages in perioperative outcomes compared with TME approach. Caution should be exercised in interpreting the differences in surgical complications between TEM and TME group due to significant heterogeneity and instability.

Current cancer treatments target tumor cells; however, the tumor microenvironment (TME) induces therapeutic resistance, tumor development and metastasis, thus rendering these treatments ineffective. Research on the TME has therefore concentrated on nonmalignant cells. Cancer-associated fibroblasts (CAFs) are a major TME component, which contribute to cancer progression due to their diverse origins, phenotypes and functions, including cancer cell invasion and migration, extracellular matrix remodeling, tumor metabolism modulation and therapeutic resistance. Standard cancer treatment typically exacerbates the senescence-associated secretory phenotype (SASP) of senescent cancer cells and nonmalignant cells that actively leak proinflammatory signals in the TME. Therapy-induced senescence may impair cancer cell activity and compromise treatment responsiveness. CAFs and SASP are well-studied in the formation and progression of cancer. The present review discusses the current data on CAF senescence caused by anticancer treatment and assesses how senescence-like CAFs affect tumor formation. The development of senolytic medication for aging stromal cells is also highlighted. Combining cancer therapies with senolytics may boost therapeutic effects and provide novel possibilities for research.

Tumor immunity is a promising topic in the area of cancer therapy. The \'soil\' function of the tumor microenvironment (TME) for tumor growth has attracted wide attention from scientists. Tumor-infiltrating immune cells in the TME, especially the tumor-infiltrating lymphocytes (TILs), serve a key role in cancer. Firstly, relevant literature was searched in the PubMed and Web of Science databases with the following key words: \'Tumor microenvironment\'; \'TME\'; \'tumor-infiltrating immunity cells\'; \'gynecologic malignancies\'; \'the adoptive cell therapy (ACT) of TILs\'; and \'TIL-ACT\' (https://pubmed.ncbi.nlm.nih.gov/). According to the title and abstract of the articles, relevant items were screened out in the preliminary screening. The most relevant selected items were of two types: All kinds of tumor-infiltrating immune cells; and advanced research on TILs in gynecological malignancies. The results showed that the subsets of TILs were various and complex, while each subpopulation influenced each other and their effects on tumor prognosis were diverse. Moreover, the related research and clinical trials on TILs were mostly concentrated in melanoma and breast cancer, but relatively few focused on gynecological tumors. In conclusion, the present review summarized the biological classification of TILs and the mechanisms of their involvement in the regulation of the immune microenvironment, and subsequently analyzed the development of tumor immunotherapy for TILs. Collectively, the present review provides ideas for the current treatment dilemma of gynecological tumor immune checkpoints, such as adverse reactions, safety, personal specificity and efficacy.

Neuroendocrine neoplasms (NENs) are a heterogenous and recurrent group of malignancies originating from neuroendocrine secretory cells diffused on all parts of the human body. Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) account for most NENs. Considering the abundance of possible origins, locations, and tumor specifications, there is still no consensus about optimal treatment options for these neoplasms. In light of the escalating immunotherapeutic approaches, it is crucial to define indications for such therapy in GEP-NETs. Bearing in mind the significance of pathophysiological mechanisms and tumor microenvironment (TME) impact on carcinogenesis, defining TME structure and correlation with the immune system in GEP-NETs appears essential. This paper aimed to assess the characterization of the tumor immune microenvironment for a better understanding of the possible therapeutic options in GEP-NETS. The authors performed a systematic review, extracting papers from the PubMed, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Among 3800 articles identified through database searching, 292 were assessed for eligibility. Ultimately, 28 articles were included in the qualitative synthesis. This paper sums up the research on the immune cell infiltrates, immune checkpoint expression, cytokine profile, neoangiogenesis, and microbiome in the TME of GEP-NETs.

Renal cell carcinoma (RCC) is the second lethal urogenital malignancy with the increasing incidence and mortality in the world. Clear cell renal cell carcinoma (ccRCC) is one major subtype of RCC, which accounts for about 70 to 80% of all RCC cases. Although many innovative therapeutic options have emerged during the last few decades, the efficacy of these treatments for ccRCC patients is very limited. To date, the prognosis of patients with advanced or metastatic ccRCC is still poor. The 5-year survival rate of these patients remains less than 10%, which mainly attributes to the complexity and heterogeneity of the tumor microenvironment (TME). It has been demonstrated that long non-coding RNAs (lncRNAs) perform an indispensable role in the initiation and progression of various tumors. They mostly function as sponges for microRNAs (miRNAs) to regulate the expression of target genes, finally influence the growth, metastasis, apoptosis, drug resistance and TME of tumor cells. However, the role of lncRNA/miRNA/mRNA axis in the TME of ccRCC remains poorly understood. In this review, we summarized the biological function of lncRNA/miRNA/mRNA axis in the pathogenesis of ccRCC, then discussed how lncRNA/miRNA/mRNA axis regulate the TME, finally highlighted their potential application as novel biomarkers and therapeutic targets for ccRCC.

Tumor‑associated macrophages (TAMs) are crucial cells of the tumor microenvironment (TME), which belong to the innate immune system and regulate primary tumor growth, immunosuppression, angiogenesis, extracellular matrix remodeling and metastasis. The review discusses current knowledge of essential cell‑cell interactions of TAMs within the TME of solid tumors. It summarizes the mechanisms of stromal cell (including cancer‑associated fibroblasts and endothelial cells)‑mediated monocyte recruitment and regulation of differentiation, as well as pro‑tumor and antitumor polarization of TAMs. Additionally, it focuses on the perivascular TAM subpopulations that regulate angiogenesis and lymphangiogenesis. It describes the possible mechanisms of reciprocal interactions of TAMs with other immune cells responsible for immunosuppression. Finally, it highlights the perspectives for novel therapeutic approaches to use combined cellular targets that include TAMs and other stromal and immune cells in the TME. The collected data demonstrated the importance of understanding cell‑cell interactions in the TME to prevent distant metastasis and reduce the risk of tumor recurrence.

Hepatocellular carcinoma (HCC), the most prevalent subtype of liver cancer, is the second main reason for cancer-related deaths worldwide. In recent decades, sufficient evidence supported that immunotherapy was a safe and effective treatment option for HCC. However, tolerance and frequent recurrence and metastasis occurred in patients after immunotherapy due to the complicated crosstalk in the tumor immunosuppressive microenvironment (TIME) in HCC. Therefore, elucidating the TIME in HCC and finding novel modulators to target TIME for attenuating immune suppression is critical to optimize immunotherapy. Recently, studies have shown the potentially immunoregulatory activities of natural compounds, characterized by multiple targets and pathways and low toxicity. In this review, we concluded the unique role of TIME in HCC. Moreover, we summarized evidence that supports the hypothesis of natural compounds to target TIME to improve immunotherapy. Furthermore, we discussed the comprehensive mechanisms of these natural compounds in the immunotherapy of HCC. Accordingly, we present a well-grounded review of the naturally occurring compounds in cancer immunotherapy, expecting to shed new light on discovering novel anti-HCC immunomodulatory drugs from natural sources.