Prognostic Relevance of Immunosuppressive CD155/TIGIT Signaling in Locally Advanced Rectal Cancer Patients With Neoadjuvant Chemoradiotherapy.

Background/aim: The CD155/TIGIT axis has recently emerged as a promising immunotherapeutic target in several malignancies. However, its prognostic relevance within the tumor microenvironment (TME) in patients with locally advanced rectal cancer (LARC) who have received neo-adjuvant chemoradiotherapy (neoCRT) remains unclarified.

Materials And Methods: The levels of tumor CD155 and TIGIT T cells in pair-matched pre-neoCRT biopsies and post-neoCRT surgical tissues were evaluated in 110 LARC tissues using immunohistochemistry.

Transvaginal natural orifice specimen extraction surgery for left-sided colorectal resection: A single-centre cohort study.

Introduction: Transvaginal natural orifice specimen extraction surgery (NOSES) is an innovative and feasible approach for left-sided colorectal resections in females. This study aimed to report our experience with transvaginal NOSES for left-sided laparoscopic colorectal resections.

Patients And Methods: We analysed data for all patients with transvaginal extraction performed for left-sided laparoscopic colorectal resections between 2011 and 2021 at a tertiary teaching hospital in Taiwan.

Characterizing Genetic Susceptibility to Colorectal Cancer in Taiwan Through Genome-Wide Association Study.

We conducted the first genome-wide association study (GWAS) of colorectal cancer (CRC) in Taiwan with 5342 cases and 61,015 controls. Ninety-two SNPs in three genomic regions reached genome-wide significance (p < 5 × 10). The lead SNPs in these three regions were: rs12778523 (OR = 1.

Transanal Minimally Invasive Surgery Versus Endoscopic Submucosal Dissection for Rectal Lesions: A Community Hospital Experience.

To compare tumor margins and surgical outcomes between transanal minimally invasive surgery (TAMIS) and endoscopic submucosal dissection (ESD) for large or malignant rectal adenomatous polyps. Single institution retrospective analysis of patients who underwent TAMIS or ESD surgery. In total, 30 consecutive patients with similar demographics who underwent either TAMIS ( = 19) or ESD ( = 11) were included.

Inhibition of DNMTs increases neoantigen-reactive T-cell toxicity against microsatellite-stable colorectal cancer in combination with radiotherapy.

The therapeutic efficacy of immunotherapy is limited in the majority of colorectal cancer patients due to the low mutational and neoantigen burdens in this immunogenically "cold" microsatellite stability-colorectal cancer (MSS-CRC) cohort. Here, we showed that DNA methyltransferase (DNMT) inhibition upregulated neoantigen-bearing gene expression in MSS-CRC, resulting in increased neoantigen presentation by MHC class I in tumor cells and leading to increased neoantigen-specific T-cell activation in combination with radiotherapy. The cytotoxicity of neoantigen-reactive T cells (NRTs) to DNMTi-treated cancer cells was highly cytotoxic, and these cells secreted high IFNγ levels targeting MSS-CRC cells after ex vivo expansion of NRTs with DNMTi-treated tumor antigens.

Neoantigen-augmented iPSC cancer vaccine combined with radiotherapy promotes antitumor immunity in poorly immunogenic cancers.

Although irradiated induced-pluripotent stem cells (iPSCs) as a prophylactic cancer vaccine elicit an antitumor immune response, the therapeutic efficacy of iPSC-based cancer vaccines is not promising due to their insufficient antigenicity and the immunosuppressive tumor microenvironment. Here, we found that neoantigen-engineered iPSC cancer vaccines can trigger neoantigen-specific T cell responses to eradicate cancer cells and increase the therapeutic efficacy of RT in poorly immunogenic colorectal cancer (CRC) and triple-negative breast cancer (TNBC). We generated neoantigen-augmented iPSCs (NA-iPSCs) by engineering AAV2 vector carrying murine neoantigens and evaluated their therapeutic efficacy in combination with radiotherapy.

Robotic versus laparoscopic pelvic lateral lymph node dissection in locally advanced rectal cancer: a systemic review and meta-analysis.

Background: There are few available studies that compare the feasibility, efficacy, and safety of robotic pelvic lateral lymph node dissection compared to laparoscopic pelvic lateral lymph node dissection (LPLND) in advanced rectal cancer. This meta-analysis aims to compare perioperative outcomes between robotic and LPLND.

Methods: We performed a systemic literature review of PubMed, Embase, and Web of Science databases.

Colorectal cancer-specific IFNβ delivery overcomes dysfunctional dsRNA-mediated type I interferon signaling to increase the abscopal effect of radiotherapy.

Background: Cancer-intrinsic type I interferon (IFN-I) production triggered by radiotherapy (RT) is mainly dependent on cytosolic double-stranded DNA (dsDNA)-mediated cGAS/STING signaling and increases cancer immunogenicity and enhances the antitumor immune response to increase therapeutic efficacy. However, cGAS/STING deficiency in colorectal cancer (CRC) may suppress the RT-induced antitumor immunity. Therefore, we aimed to evaluate the importance of the dsRNA-mediated antitumor immune response induced by RT in patients with CRC.

Activation of STING by the novel liposomal TLC388 enhances the therapeutic response to anti-PD-1 antibodies in combination with radiotherapy.

Current immune checkpoint inhibiters (ICIs) have contrasting clinical results in poorly immunogenic cancers such as microsatellite-stable colorectal cancer (MSS-CRC). Therefore, understanding and developing the combinational therapeutics for ICI-unresponsive cancers is critical. Here, we demonstrated that the novel topoisomerase I inhibitor TLC388 can reshape the tumor immune landscape, corroborating their antitumor effects combined with radiotherapy as well as immunotherapy.

Effect of autologous dendritic cell cytokine-induced killer on refractory metastatic colorectal cancer: a matched case-control comparative study.

Background: Patients with metastatic colorectal cancer (mCRC) who are refractory to two or more lines of systemic chemotherapy have limited therapeutic options. The aim of this study was to evaluate the effect of autologous dendritic cell cytokine-induced killer (DC-CIK) transfer on the survival of patients with mCRC who are refractory or intolerant to at least two lines of systemic chemotherapies.

Methods: A matched case-control comparative study was conducted with patients who received DC-CIK immunotherapy in addition to standard chemotherapy (cases) and those with standard chemotherapy alone (controls).

Dual Inhibition of B7-H3 and EGFR Overcomes Acquired Chemoresistance in Colon Adenocarcinoma.

Despite advances in therapeutic strategies for colorectal cancer (CRC), CRC has a high disease incidence with significant morbidity and mortality worldwide. Notably, immunotherapy has shown limited efficacy in treating metastatic CRC, underscoring the need for alternative immunotherapeutic targets for the management of metastatic colorectal cancer (mCRC). In the present study, we evaluated the levels of the immune checkpoint proteins PD-L1, PD-L2 and B7-H3 in a large cohort retrospective study.

Prognostic Value of Immune Cells Subsets Within the Tumor Microenvironment in Patients With Rectal Adenocarcinoma.

Background/aim: One-third of newly diagnosed colorectal cancer cases are rectal cancers. Multimodal treatment regimens including surgery, radiotherapy, and chemotherapy improve local control and survival outcome and decrease tumor relapse for patients with rectal adenocarcinoma (READ). However, stratification of patients to predict their responses is urgently needed to improve therapeutic responses.

Re-evaluating the role of pelvic radiation in the age of modern precision medicine and systemic therapy.

The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC ( 2019; 37: 3223-3233), NCT04165772 ( 2022; 386: 2363-2376), and PROSPECT ( 2023; 389: 322-334). In this review, we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.

TNFα modulates PANX1 activation to promote ATP release and enhance P2RX7-mediated antitumor immune responses after chemotherapy in colorectal cancer.

ATP and its receptor P2RX7 exert a pivotal effect on antitumor immunity during chemotherapy-induced immunogenic cell death (ICD). Here, we demonstrated that TNFα-mediated PANX1 cleavage was essential for ATP release in response to chemotherapy in colorectal cancer (CRC). TNFα promoted PANX1 cleavage via a caspase 8/3-dependent pathway to enhance cancer cell immunogenicity, leading to dendritic cell maturation and T-cell activation.

Neoadjuvant Chemotherapy With/Without Radiotherapy for Locally Advanced Rectal Cancer: A Nationwide Retrospective Cohort Study.

Background/aim: The role of neoadjuvant radiotherapy in the management of patients with locally advanced rectal cancer (LARC) who have undergone neoadjuvant systemic therapy has been the subject of recent debate.

Patients And Methods: We identified eligible rectal cancer patients diagnosed between 2011 and 2020 using data from the Taiwan Cancer Registry. In our primary analysis, we applied propensity score weighting (PSW) to balance observable potential confounders.

Dysfunctional TLR1 reduces the therapeutic efficacy of chemotherapy by attenuating HMGB1-mediated antitumor immunity in locally advanced colorectal cancer.

Regional lymph node metastasis is an important predictor for survival outcome and an indicator for postoperative adjuvant chemotherapy in patients with colorectal cancer. Even with advances in adjuvant chemotherapeutic regimens, 5-year distant metastasis and survival rates are still unsatisfactory. Here, we evaluate the clinical significance of polymorphisms in receptors for HMGB1, which is the hallmark of chemotherapy-induced immunogenic cell death, in patients with stage II-III colon carcinoma (COAD).

Evaluation of the Prognostic Value of Low-Frequency KRAS Mutation Detection in Circulating Tumor DNA of Patients with Metastatic Colorectal Cancer.

mutation in tumor tissue is a well-known predictor of resistance to the treatment of anti-EGFR antibodies in metastatic colorectal cancers (mCRC). However, the prognostic value of low-frequency plasma circulating tumor DNA (ctDNA) mutation in predicting treatment resistance in pretreated mCRC patients remains controversial. This study retrospectively reviewed the clinical course, including response to anti-EGFR and anti-VEGF therapies, and changes in serum tumor marker levels along with image studies in mCRC patients with <1.

Impact of Pattern Recognition Receptors on the Prognosis of Chemotherapy-treated Rectal Cancer Patients.

Background/aim: Chemotherapeutic drugs or radiation can cause immunogenic cell death (ICD) and damage-associated molecular pattern (DAMP) release to activate pattern recognition receptor (PRR) in immune cells. Several PRRs bridge innate immunity and adaptive immunity and are implicated in the anticancer immune response. However, single nucleotide polymorphisms (SNPs) in PRRs are associated with chemotherapeutic drugs or radiation response in cancer treatment.

Pelvic Neoadjuvant Radiotherapy for Stage M1a Rectal Adenocarcinoma Patients Treated With Systemic Therapy Followed by Proctectomy and Metastasectomy: A Nationwide Retrospective Cohort Study.

Background/aim: The effect of pelvic neoadjuvant radiotherapy (nRT) for stage M1a rectal adenocarcinoma patients treated with systemic therapy followed by proctectomy and metastasectomy was scarcely investigated in the literatures.

Patients And Methods: The eligible rectal cancer patients diagnosed between 2011-2019 were identified via the Taiwan Cancer Registry. In the primary analysis, we used propensity score weighting to balance observable potential confounders and compared the hazard ratio (HR) of death for the nRT group vs.

Acupuncture May Help to Prevent Chemotherapy-Induced Peripheral Neuropathy: A Randomized, Sham-Controlled, Single-Blind Study.

Objective: This study investigated the efficacy of acupuncture in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with colorectal cancer (CRC).

Methods: This single center, randomized, controlled, single-blind clinical trial randomly assigned patients with stage 3 CRC attending outpatient clinics in China Medical University Hospital to either verum or sham acupuncture treatment concurrently with chemotherapy. Primary outcomes were nerve conduction velocity (NCV) and touch thresholds of limb terminals.

Targeting CD73 increases therapeutic response to immunogenic chemotherapy by promoting dendritic cell maturation.

The CD39-CD73-adenosinergic pathway converts adenosine triphosphate (ATP) to adenosine for inhibiting anti-tumor immune responses. Therefore, targeting CD73 to reinvigorate anti-tumor immunity is considered the novel cancer immunotherapy to eradicate tumor cells. To fully understand the critical role of CD39/CD73 in colon adenocarcinoma (COAD), this study aims to comprehensive investigate the prognostic significance of CD39 and CD73 in stage I-IV COAD.

A Novel Engineered AAV-Based Neoantigen Vaccine in Combination with Radiotherapy Eradicates Tumors.

The potency of tumor-specific antigen (TSA) vaccines, such as neoantigen (neoAg)-based cancer vaccines, can be compromised by host immune checkpoint inhibitory mechanisms, such as programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1), that attenuate neoAg presentation on dendritic cells (DC) and hinder T cell-mediated cytotoxicity. To overcome PD-1/PD-L1 inhibition in DCs, we developed a novel adeno-associated virus (meAAV) neoAg vaccine, modified with TLR9 inhibitory fragments, PD-1 trap, and PD-L1 miRNA, which extend the persistence of meAAV and activate neoAg-specific T-cell responses in immune-competent colorectal and breast cancer murine models. Moreover, we found that in combination with radiotherapy, the meAAV-based neoAg cancer vaccine not only elicited higher antigen presentation ability, but also maintained neoAg-specific cytotoxic T lymphocyte (CTL) responses.

Laparoscopic versus open emergent colectomy for ischemic colitis: a propensity score-matched comparison.

Introduction: Laparoscopic colectomy is rarely performed for ischemic colitis. The aim of this propensity score-matched study was to compare preoperative characteristics, intraoperative details and short-term outcomes for emergent laparoscopic colectomy versus the traditional open approach for patients with ischemic colitis.

Methods: Retrospective review of 96 patients who underwent emergent colectomy for ischemic colitis between January 2011 and December 2020 (39 via laparoscopy, 57 via laparotomy) was performed.