Neoadjuvant camrelizumab plus apatinib for locally advanced microsatellite instability-high or mismatch repair-deficient colorectal cancer (NEOCAP): a single-arm, open-label, phase 2 study.

Background: PD-1 blockade is highly efficacious for mismatch repair-deficient colorectal cancer in both metastatic and neoadjuvant settings. We aimed to explore the activity and safety of neoadjuvant therapy with PD-1 blockade plus an angiogenesis inhibitor and the feasibility of organ preservation in patients with locally advanced mismatch repair-deficient colorectal cancer.

Methods: We initiated a single-arm, open-label, phase 2 trial (NEOCAP) at Sun Yat-sen University Cancer Center and the Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China.

Long-Term Outcomes of dMMR/MSI-H Rectal Cancer Treated With Anti-PD-1-Based Immunotherapy as Curative-Intent Treatment.

Background: Neoadjuvant anti-PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti-PD-1 therapy.

Methods: We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti-PD-1-based treatment from 4 Chinese medical centers.

Efficacy of PD-1 inhibitors for colorectal cancer and polyps in Lynch syndrome patients.

Background: Programmed death-1 (PD-1) inhibitor is effective for colorectal cancer (CRC) with deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H). We aimed to explore its effects on CRCs and colonic polyps in Lynch syndrome (LS) patients.

Methods: LS patients with CRC who had evaluable tumours and received at least 2 cycles of PD-1 inhibitors were retrospectively included.

Neoadjuvant Immunotherapy Leads to Major Response and Low Recurrence in Localized Mismatch Repair-Deficient Colorectal Cancer.

Background: Our study aimed to evaluate the efficacy and feasibility of neoadjuvant anti-PD-1 treatment for localized mismatch repair-deficient (dMMR) colorectal cancer (CRC).

Patients And Methods: The study cohort included patients with localized dMMR CRC who received PD-1 inhibitors as neoadjuvant therapy from 3 medical centers in Southern China. Main eligibility criteria included age between 18 and 75 years, ECOG performance status of 0 or 1, and receipt of ≥2 doses of PD-1 inhibitors.

Longest survival with primary intracranial malignant melanoma: A case report and literature review.

Background: Primary intracranial malignant melanoma (PIMM) is rare, and its prognosis is very poor. It is not clear what systematic treatment strategy can achieve long-term survival. This case study attempted to identify the optimal strategy for long-term survival outcomes by reviewing the PIMM patient with the longest survival following comprehensive treatment and by reviewing the related literature.

Anti-PD-1-based immunotherapy as curative-intent treatment in dMMR/MSI-H rectal cancer: A multicentre cohort study.

Background: In a portion of patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer, clinical complete response (cCR) could be achieved after anti-programmed cell death protein 1 (anti-PD-1) immunotherapy. However, no data are available concerning the safety of omitting surgery and adopting immunotherapy as a curative-intent treatment for these patients.

Methods: We retrospectively collected a series of patients with dMMR/MSI-H rectal adenocarcinoma who had cCR after receiving anti-PD-1 immunotherapy and adopted immunotherapy as curative-intent treatment from six institutions.

HHLA2 predicts improved prognosis of anti-PD-1/PD-L1 immunotherapy in patients with melanoma.

Background: As a recognized highly immunogenic tumor, immune checkpoint blockades (ICB) have been widely used as a systemic treatment option for melanoma. However, only about half of treated patients could benefit from it in Caucasians, and only about 15% in Chinese melanoma patients. Robust predictive biomarkers are needed.

Phase I study of adjuvant immunotherapy with autologous tumor-infiltrating lymphocytes in locally advanced cervical cancer.

BACKGROUNDAdoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has achieved remarkable clinical efficacy in metastatic cancers such as melanoma and cervical cancer (CC). Here, we explored the safety, feasibility, and preliminary tumor response and performed translational investigations of adjuvant immunotherapy using infusion of autogenous TILs (auto-TILs) following concurrent chemoradiotherapy (CCRT) in patients with CC who had locally advanced disease.METHODSTwenty-seven patients with CC with stage III-IV disease were recruited in this single-center, phase I study.

Neoadjuvant Immune Checkpoint Inhibition Improves Organ Preservation in T4bM0 Colorectal Cancer With Mismatch Repair Deficiency: A Retrospective Observational Study.

Background: Colorectal cancer with mismatch repair deficiency is usually less aggressive and associated with a lower risk of distant metastasis. Immune checkpoint inhibition, rather than traditional chemoradiotherapy, has shown great advantages in treating such patients.

Objective: This study aimed to verify the hypothesis that locally very advanced (T4b) colorectal cancer without distant metastases might present with higher probability of mismatch repair deficiency and be more sensitive to neoadjuvant immune checkpoint inhibition.

An Evidence-Based Staging System for Mucosal Melanoma: A Proposal.

Background: There is no widely employed staging system for mucosal melanoma (MuM) that incorporates all anatomic sites. We hypothesized that MuM patients arising from different anatomical sites could be staged using a common approach.

Methods: A prospective database contained 1814 MuM patients with a median follow-up of 5.

The ratio of preoperative alpha-fetoprotein level to total tumor volume as a prognostic factor of hepatocellular carcinoma after liver transplantation.

To evaluate the effect of preoperative serum alpha-fetoprotein(AFP) level to total tumor volume (TTV) ratio as a prognostic marker on predicting the tumor recurrence and overall survival time of patients with hepatocellular carcinoma (HCC) after liver transplantation.One-hundred eight patients with HCC who underwent liver transplantation in Beijing Chaoyang Hospital from April 2013 to October 2017 were studied. Divided into AFP/TTV≤2 group and AFP/TTV>2 group by the best cut-off score calculated by receiver operation characteristic curve, the clinical and pathological data of the patients in two groups were compared to explore the relationship between AFP/TTV and tumor recurrence together with the prognosis of HCC patients after liver transplantation.

Efficacy and safety of anti-PD-1 inhibitor combined with nab-paclitaxel in Chinese patients with refractory melanoma.

Purpose: This retrospective study aimed to evaluate the combined effect of anti-PD-1 inhibitor and nanoparticle albumin-bound (nab)-paclitaxel for refractory melanoma among Chinese patients.

Methods: Data from January 2018 to March 2021 were retrospectively collected and analyzed. Sixty-four patients were eligible for analysis from a single Chinese cancer center.

Safety and Tolerability of BRAF Inhibitor and BRAF Inhibitor-Based Combination Therapy in Chinese Patients With Advanced Melanoma: A Real World Study.

The toxicity spectrum between Chinese and Caucasian patients with melanoma who were treated with BRAF inhibitors (BRAFi) may differ. The purpose of the present study was to assess the safety and tolerability of BRAFi and BRAFi-based combination therapies [MEK inhibitors (MEKi) or anti-programmed death-1 (PD-1) antibody] in Chinese patients with mutation-positive metastatic melanoma. We also investigated whether treatment-related adverse events (AEs) correlated with the prognosis.

Hypoxia Induces Mitochondrial Defect That Promotes T Cell Exhaustion in Tumor Microenvironment Through MYC-Regulated Pathways.

T cell exhaustion is an obstacle to immunotherapy for solid tumors. An understanding of the mechanism by which T cells develop this phenotype in solid tumors is needed. Here, hypoxia, a feature of the tumor microenvironment, causes T cell exhaustion (T) by inducing a mitochondrial defect.

Galectin-9 promotes a suppressive microenvironment in human cancer by enhancing STING degradation.

Galectin-9 (Gal-9) is known to enhance the expansion of myeloid-derived suppressor cells (MDSCs) in murine models. Its contribution to the expansion of MDSCs in human malignancies remain to be investigated. We here report that Gal-9 expression in nasopharyngeal carcinoma (NPC) cells enhances the generation of MDSCs (CD33CD11bHLA-DR) from CD33 bystander cells.

Association between immune-related adverse events and efficacy of PD-1 inhibitors in Chinese patients with advanced melanoma.

Programmed cell death 1 (PD-1) checkpoint inhibitor therapy leads to immune-related adverse events (irAEs). We sought to evaluate whether the development of irAEs correlates with the treatment response in Chinese patients with advanced melanoma. In this study, we conducted a retrospective study of advanced melanoma patients who received PD-1 inhibitor therapy in China between August 2014 and March 2018.

PD-1 blockade in neoadjuvant setting of DNA mismatch repair-deficient/microsatellite instability-high colorectal cancer.

: Although PD-1 blockade has significantly improved the survival of metastatic colorectal cancer with DNA Mismatch Repair-Deficient/Microsatellite Instability-High (MSI-H), the data on neoadjuvant setting is limited. : In this retrospective study, we enrolled eight patients with advanced MSI-H colorectal cancer from three hospitals. Four patients are locally advanced and four are metastatic.

Down Regulation of c-FLIP Enhance PD-1 Blockade Efficacy in B16 Melanoma.

Immune checkpoint blockade of programmed cell death protein 1 (PD-1) had an impressive long-lasting effect in a portion of advanced-stage melanoma patients, however, this therapy failed to induce responses in several patients; how to increase the objective response rate is very important. Cellular FLICE-inhibitory protein (c-FLIP) could inhibit apoptosis directly at the death-inducing signaling complex of death receptors and is also considered to be the main cause of immune escape. The overexpression of c-FLIP occurs frequently in melanoma and its expression is associated with the prognosis.

Prognostic Factors and Recurrence Patterns in T4 Gastric Cancer Patients after Curative Resection.

: To investigate prognostic factors and recurrence patterns in T4 gastric cancer (GC) patients after curative resection. : Between January 2004 and December 2014, 249 patients with T4 gastric cancer undergoing curative resection were recruited. Patient characteristics, survival, prognostic factors and recurrence patterns were analyzed.

STING signaling remodels the tumor microenvironment by antagonizing myeloid-derived suppressor cell expansion.

Stimulator of interferon genes (STING), a major adaptor protein in antiviral innate immune signaling, is considered as one of the most important regulators of antiviral and antitumor immunity. Although STING agonists are now intensively studied in clinical trials as a new class of adjuvants to boost cancer immunotherapy, the tumor-intrinsic role of the STING pathway in shaping the tumor microenvironment remains controversial. Here, we discovered that STING plays a vital role in regulation of myeloid-derived suppressor cell (MDSC) differentiation and antitumor immunity in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC).

Sphingosine 1 phosphate receptor-1 (S1P1) promotes tumor-associated regulatory T cell expansion: leading to poor survival in bladder cancer.

Regulatory T cells (Tregs) represent an important contributor to cancer immune escape, but the molecular mechanism responsible for Treg expansion in tumors is heterogeneous and unclear. Here, we investigated the role of S1P1, a receptor of the bioactive lipid sphingosine 1-phosphate (S1P), in regulating the crosstalk between tumor cells and tumor-associated Tregs in bladder cancer (BC). We found that the frequency of CD4Foxp3 Tregs was increased in circulating and tumor-infiltrating lymphocytes from BC patients.

Efficacy and safety of primary surgery with postoperative radiotherapy in head and neck mucosal melanoma: a single-arm Phase II study.

Background: There still remains no well-established treatment strategy for head and neck mucosal melanoma (HNMM). We aim to evaluate the effectiveness and safety of primary surgery with postoperative radiotherapy for this disease.

Patients And Methods: A single-arm, Phase II clinical trial was conducted at Sun Yat-Sen University Cancer Center.

Tumour YAP1 and PTEN expression correlates with tumour-associated myeloid suppressor cell expansion and reduced survival in colorectal cancer.

The expansion of myeloid-derived suppressor cells (MDSCs) correlates with tumorigenesis in colorectal cancer (CRC). Here, we found a significant association between CD33 MDSC number and Yes-associated protein 1 (YAP1) and phosphatase and tensin homologue (PTEN) levels in CRC patients (P < 0·05). Moreover, the CD33 MDSCs, YAP1 and PTEN were identified as predictors for the prognosis of CRC patients (P < 0·05).