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Abstrcat: Basal cell carcinoma (BCC) of the prostate is a rare and enigmatic tumor with uncertain biological behavior and treatment modalities. Some studies suggest that BCC exhibits invasive characteristics and a high degree of malignancy, necessitating proactive management and vigilant monitoring. Notably, there is a lack of reported effective treatment utilizing programmed cell death protein-1 (PD-1) inhibitors for advanced BCC of the prostate. This study explores the efficacy of tislelizumab, as a single-agent therapy, in the successful treatment of advanced prostate BCC.

Background: The efficacy of immunotherapy plus neoadjuvant chemotherapy and concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal carcinoma (LA-NPC) has not been reported. This study retrospectively compared the efficacy of tislelizumab plus neoadjuvant chemotherapy and CCRT with neoadjuvant chemotherapy followed by CCRT. Methods: Ninety patients with stages III–IVa NPC were identified between January 2020 and March 2021 at the Affiliate Hospital of Guangdong Medical University. Forty-three patients in the observation group (OG) received tislelizumab plus nano albumin–paclitaxel and cisplatin (nab-TP) regimen, followed by CCRT, while forty-seven patients in the control group (CG) received nab-TP regimen followed by CCRT. Results: The complete response rate after neoadjuvant therapy was significantly higher in the OG compared to the CG (37.2% vs. 12.8 %). The objective response rates were 88.4 % in the OG and 70.2 % in the CG. The 3-year progression-free survival (PFS) rates for OG and CG patients were 93.0 % and 78.7 %, respectively (P = 0.04, HR = 0.31). The overall survival (OS) rates for the OG and the CG were 95.3 % and 87.2 %, respectively (P = 0.15, HR = 0.36). Locoregional relapse-free survival (LRFS) rates were 90.7 % for the OG and 72.3 % for the CG (P = 0.04, HR = 0.38), and distant metastasis-free survival (DMFS) rates were 95.3 % for the OG, and 80.9 % for the CG (P = 0.04, HR = 0.30). For PD-L1 high-expression and low-expression rates, the 3-year PFS rates were 89.2 % and 85.7 % (P = 0.77, HR = 1.21), and the OS rates were 90.2 % and 89.2 % (P = 0.65, HR = 1.36), respectively. Conclusion: Tislelizumab combined with neoadjuvant chemotherapy and CCRT showed encouraging therapeutic effects and good tolerability in patients with LA-NPC compared to the standard treatment.

In recent years, with the in-depth study of PD-1/PD-L1 related pathways, great progress has been made in cancer immunotherapy. However, the immunotherapy regimen for mccRCC is still controversial in clinical practice.A 50-year-old man with mccRCC complicated with renal venous tumor thrombus from 2019 to present, including surgical treatment, targeted therapy and the combined treatment regimen of “Tislelizumab combined with Sunitinib”. Although he experienced a roller coaster of adverse reactions during treatment, the patient's prognosis was good.Tislelizumab combined with Sunitinib is safe and effective in the Treatment of mccRCC.

Summary: Background: Immunotherapy has revolutionized the treatment of cancer. However, microsatellite stable (MSS) metastatic colorectal cancer (mCRC) shows a low response to PD-1 inhibitors. Antiangiogenic therapy can enhance anti-PD-1 efficacy, but it still cannot meet clinical needs. Increasing evidence supported a close relationship between gut microbiome and anti-PD-1 efficacy. This study aimed to explore the efficacy and safety of the combination of fecal microbiota transplantation (FMT) and tislelizumab and fruquintinib in refractory MSS mCRC. Methods: In the phase II trial, MSS mCRC patients were administered FMT plus tislelizumab and fruquintinib as a third-line or above treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), clinical benefit rate (CBR), safety and quality of life. Feces and peripheral blood were collected for exploratory biomarker analysis. This study is registered with Chictr.org.cn, identifier ChiCTR2100046768. Findings: From May 10, 2021 to January 17, 2022, 20 patients were enrolled. Median follow-up was 13.7 months. Median PFS was 9.6 months (95% CI 4.1–15.1). Median OS was 13.7 months (95% CI 9.3–17.7). Median DoR was 8.1 months (95% CI 1.7–10.6). ORR was 20% (95% CI 5.7–43.7). DCR was 95% (95% CI 75.1–99.9). CBR was 60% (95% CI 36.1–80.9). Nineteen patients (95%) experienced at least one treatment-related adverse event (TRAE). Six patients (30%) had grade 3–4 TRAEs, with the most common being albuminuria (10%), urine occult blood (10%), fecal occult blood (10%), hypertension (5%), hyperglycemia (5%), liver dysfunction (5%), hand-foot skin reaction (5%), and hypothyroidism (5%). No treatment-related deaths occurred. Responders had a high-abundance of Proteobacteria and Lachnospiraceae family and a low-abundance of Actinobacteriota and Bifidobacterium. The treatment did not change the structure of peripheral blood TCR repertoire. However, the expanded TCRs exhibited the characteristics of antigen-driven responses in responders. Interpretation: FMT plus tislelizumab and fruquintinib as third-line or above treatment showed improved survival and manageable safety in refractory MSS mCRC, suggesting a valuable new treatment option for this patient population. Funding: This study was supported by the National Natural Science Foundation of China (82102954 to Wensi Zhao) and the Special Project of Central Government for Local Science and Technology Development of Hubei Province (ZYYD2020000169 to Yongshun Chen).

Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare pathological type of non-small cell lung cancer, only occurs in 0.1%–0.4 % of lung cancer patients. It has a poor prognosis and shows low response to conventional chemotherapy. Target therapy, immunotherapy, and other new approaches are worth exploring in PSC. Recently, patients with MET ex14 skipping mutation can obtain good therapeutic efficacy through target therapy. But there was no definitive treatment for patients without this special mutation. Case description: Now, we report a female PSC patient without MET ex14 skipping mutation in the cT4N2M1 stage treated with Tislelizumab and Anlotinib obtained remarkable effect for more than 2 years. Significantly, in this case, immunotherapy and antiangiogenic therapy continued to prolong the survival time of more than 10 months for the patient after being treated by local radiotherapy. This is the first case that reported the effectiveness of immunotherapy and antiangiogenic therapy combined with local radiotherapy in treating PSC and achieved more long-term clinical efficacy than other treatments. Conclusions: Thus, immunotherapy and antiangiogenic therapy combined with local radiotherapy may bring new hope to advanced PSC patients and is worth conducting further research. It provided an effective reference for the treatment of advanced PSC patients without METex14 skipping mutation. Moreover, this case also demonstrated the synergistic effect of radiotherapy and immunotherapy.

As a DNA mismatch repair deficit (dMMR) anticancer medication, and a humanized monoclonal antibody (hmAb), Tislelizumab has attracted significant interest in recent years. The programmed cell death protein-1 (PD-1) and its ligands (PD-L1/CD274/B7-H1 and PDL2/CD273) may bind to each other with great affinity. This binding prevents activated T-cells from continuing to proliferate, produce cytokines, and engage in cytotoxic action. The B7:PD-1 inhibitory immunological checkpoint receptor binds to the B7-2(CD86) B-lymphocyte activation antigen. This paper presents Tislelizumab's molecular docking and dynamics simulations with the receptor B7-2(CD86) and its downstream signaling proteins CTLA-4 and IL-6. When docked to B cell stimulatory factor-2 soluble IL-6 receptor alpha (sIL6Ra/CD126), Tislelizumab had a strong binding affinity of 329 kcal/mol and provided an excellent quality model with an LGscore of 4.54. The type I membrane protein B7-2(CD86), a member of the immunoglobulin superfamily, responded to docking with an affinity of −332.35 kcal/mol and LGscore of 2.54. Docking to the immune checkpoint protein receptor cytotoxic T-lymphocyte-associated protein-4 (CTLA-4/CD152) had a binding affinity of −305.91 kcal/mol, facilitating immunological control and cellular dissociation. Tislelizumab and these target proteins exhibited persistent and advantageous interactions in molecular dynamics studies. The STRING functional protein-protein network analysis supported our in silico docking and dynamic simulation results. This analysis also included comparisons of the binding modes of mAbs to protein receptors involved in the cancer hallmark mechanism(s), demonstrating that IL-6, B7-2, and CTLA-4 act and are inhibited in group-mode. Functional enrichment analysis and molecular modelling supported the relationship between the hallmarks of the tumor microenvironment that link inflammation to immunity. Tislelizumab may therefore be able to prevent these three proteins from acting. These findings may also shine light on Dostarlimab's mode of action, which in 2022 achieved ground-breaking success in a clinical study for colorectal cancer.

Purpose: To evaluate the effectiveness and safety of low-dose gemcitabine and metronomic capecitabine in combination with tislelizumab for patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) who have previously received other anti-PD-1 therapies., Methods: This retrospective, observational study included patients with RM-NPC who had prior treatment with anti-PD-1 therapy and subsequently received tislelizumab along with low-dose gemcitabine and metronomic capecitabine between March 2019 and August 2023. Progression-free survival (PFS) was estimated using the Kaplan-Meier method., Results: Among 25 eligible patients, 8 (20%) achieved a complete response (CR). The objective response rate (ORR) was 68%, and the disease control rate (DCR) was 80%. The 1-year PFS rate was 78%. All patients experienced treatment-related adverse events, which were all grade 1 or 2., Conclusion: The combination of tislelizumab with low-dose gemcitabine and metronomic capecitabine demonstrated promising antitumor effectiveness in RM-NPC patients who had failed previous anti-PD-1 therapy, with a manageable safety profile., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: First-line tislelizumab plus chemotherapy significantly improved progression-free survival (PFS) versus chemotherapy alone in advanced squamous non-small-cell lung cancer (sq-NSCLC) at the interim analysis of the phase III RATIONALE-307 trial. We present the final analysis of this trial., Patients and Methods: Patients with treatment-naive, stage IIIB/IV, sq-NSCLC were randomized (1 : 1: 1) to 21-day cycles of i.v.: tislelizumab plus paclitaxel and carboplatin (arm A); tislelizumab plus nab-paclitaxel and carboplatin (arm B); or paclitaxel and carboplatin (arm C). The primary endpoint was independent review committee-assessed PFS; overall survival was a secondary endpoint., Results: In total, 360 patients were randomized; 355 received treatment. At the final analysis (median study follow-up: 16.7 months), tislelizumab plus chemotherapy had a manageable safety profile, consistent with that at the interim analysis. Improvement in PFS was maintained for arms A and B versus C {hazard ratio (HR) 0.45 [95% confidence interval (CI) 0.33-0.62] and 0.43 (95% CI 0.31-0.60), respectively}. Overall survival HRs for arms A and B versus C were 0.68 (95% CI 0.46-1.01) and 0.75 (95% CI 0.50-1.12), respectively., Conclusions: The RATIONALE-307 final analysis demonstrated superior clinical benefit with addition of tislelizumab to chemotherapy, and a manageable safety profile, as first-line treatment of advanced sq-NSCLC., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The purpose of this study was to report an updated, final analysis with longer follow-up for the open-label phase III RATIONALE-304 study of first-line tislelizumab plus chemotherapy versus chemotherapy alone for advanced nonsquamous non-small-cell lung cancer (nsq-NSCLC)., Materials and Methods: Patients with histologically confirmed stage IIIB/IV nsq-NSCLC were randomized (2 : 1) to 4-6 cycles of tislelizumab plus platinum-based chemotherapy and pemetrexed every 3 weeks, followed by maintenance tislelizumab and pemetrexed, or platinum-based chemotherapy and pemetrexed alone every 3 weeks followed by maintenance pemetrexed. The primary endpoint was independent review committee (IRC)-assessed progression-free survival (PFS IRC ). Overall survival (OS), safety, and tolerability were secondary endpoints., Results: Overall, 334 patients were randomized (tislelizumab plus chemotherapy: n = 223; chemotherapy: n = 111). At final analysis (median follow-up 16.1 months), safety/tolerability profiles in both arms were consistent with the interim analysis. Tislelizumab plus chemotherapy continued to demonstrate prolongation of PFS IRC versus chemotherapy alone {stratified hazard ratio (HR) 0.63 [95% confidence interval (CI) 0.47-0.86]; median PFS IRC 9.8 months (95% CI 8.9-11.7 months) versus 7.6 months (95% CI 5.6-8.0 months), respectively}. OS stratified HR for tislelizumab plus chemotherapy versus chemotherapy was 0.90 (95% CI 0.63-1.28), with median OS of 21.4 months (95% CI 17.7 months-not estimable) versus 21.3 months (95% CI 15.6 months-not estimable), respectively. At a subsequent ad hoc analysis (median follow-up 19.3 months), OS HR between arms was 0.85 (95% CI 0.63-1.14); when adjusted for crossover using the two-stage method, the OS HR was 0.68 (95% CI 0.48-0.96)., Conclusions: After longer follow-up, first-line tislelizumab plus chemotherapy continued to demonstrate a manageable safety profile and a favorable PFS benefit over chemotherapy alone in patients with advanced/metastatic nsq-NSCLC., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Extensive-stage SCLC (ES-SCLC) prognosis remains poor. The phase 3 RATIONALE-312 study aimed to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line treatment for ES-SCLC., Methods: RATIONALE-312 is a randomized, double-blind, placebo-controlled trial, conducted in the People's Republic of China. Eligible patients with previously untreated ES-SCLC were randomized 1:1 to receive four cycles of tislelizumab 200 mg or placebo, with etoposide plus carboplatin or cisplatin intravenously every 3 weeks, followed by tislelizumab 200 mg or placebo as maintenance. The primary end point was overall survival (OS). Secondary end points included progression-free survival and safety., Results: Between July 22, 2019 and April 21, 2021, 457 patients were randomized to tislelizumab (n = 227) or placebo (n = 230), plus chemotherapy. Baseline demographics were generally balanced between arms. At the data cutoff (April 19, 2023), the median study follow-up was 14.2 months (interquartile range: 8.6-25.3). Tislelizumab plus chemotherapy exhibited a statistically significant OS benefit versus placebo plus chemotherapy (stratified hazard ratio = 0.75 [95% confidence interval (CI): 0.61-0.93]; one-sided p = 0.0040; median: 15.5 [95% CI: 13.5-17.1] versus 13.5 mo [95% CI: 12.1-14.9], respectively). Progression-free survival was significantly improved in the tislelizumab versus placebo arm (stratified hazard ratio = 0.64 [95% CI: 0.52-0.78]; p < 0.0001; median: 4.7 [95% CI: 4.3-5.5] versus 4.3 mo [95% CI: 4.2-4.4], respectively). Grade greater than or equal to 3 treatment-related adverse events were reported in 86% of patients in each treatment arm and were mostly hematologic., Conclusions: Tislelizumab plus chemotherapy exhibited statistically significant clinical benefit and manageable safety compared with placebo plus chemotherapy as first-line treatment in patients with advanced ES-SCLC., Competing Interests: Disclosure Dr. Zhao reports receiving payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Roche, AstraZeneca, Merck Sharp & Dohme, Novartis, and Eli Lilly. Drs. Qin and Zheng are employees of BeiGene (Beijing) Co., Ltd. and have stock or stock options with BeiGene (Beijing) Co., Ltd. Dr. Leaw and Ms. Chen are employees of BeiGene (Shanghai) Co., Ltd. and have stock or stock options with BeiGene (Shanghai) Co., Ltd. The remaining authors declare no conflict of interest., (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Background: The phase III RATIONALE-302 study evaluated tislelizumab, an anti-programmed cell death protein 1 antibody, as second-line (2L) treatment for advanced/metastatic esophageal squamous cell carcinoma (ESCC). This prespecified exploratory analysis investigated outcomes in patients from Europe and North America (Europe/North America subgroup)., Patients and Methods: Patients with tumor progression during/after first-line systemic treatment were randomized 1 : 1 to open-label tislelizumab or investigator's choice of chemotherapy (paclitaxel, docetaxel, or irinotecan)., Results: The Europe/North America subgroup comprised 108 patients (tislelizumab: n = 55; chemotherapy: n = 53). Overall survival (OS) was prolonged with tislelizumab versus chemotherapy (median: 11.2 versus 6.3 months), with a hazard ratio (HR) of 0.55 [95% confidence interval (CI) 0.35-0.87]; HR was similar irrespective of programmed death-ligand 1 score [≥10%: 0.47 (95% CI 0.18-1.21); <10%: 0.55 (95% CI 0.30-1.01)]. Median progression-free survival was 2.3 versus 2.7 months with tislelizumab versus chemotherapy [HR: 0.97 (95% CI 0.64-1.47)]. Overall response rate was greater with tislelizumab (20.0%) versus chemotherapy (11.3%), with more durable response (median duration of response: 5.1 versus 2.1 months). Tislelizumab had a favorable safety profile versus chemotherapy, with fewer patients experiencing ≥grade 3 treatment-related adverse events (13.0% versus 51.0%). Those on tislelizumab experienced less deterioration in health-related quality of life, physical functioning, and/or disease- and treatment-related symptoms (i.e. fatigue, pain, and eating problems) as compared to those on chemotherapy, per the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and QLQ-OES18 scores., Conclusions: As a 2L therapy for advanced/metastatic ESCC, tislelizumab improved OS and had a favorable safety profile as compared to chemotherapy in European/North American ESCC patients in the randomized phase III RATIONALE-302 study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: High rate of recurrence impaired the prognosis of hepatocellular carcinoma (HCC) after surgery. We aimed to explore the safety and efficacy of neoadjuvant drug-eluting bead transarterial chemoembolization (D-TACE) and tislelizumab therapy for resectable or borderline resectable HCC., Methods: 41 HCC patients received neoadjuvant therapy and surgery were respectively enrolled. The safety and efficacy of the neoadjuvant therapy were assessed. The prognosis was evaluated and compared with that of 41 matched HCC patients who received surgery alone., Results: 36 (87.8%) patients had adverse events (AEs) and only one patient had a grade 3/4 of ALT elevated. All patients performed surgery successfully and no severe postoperative complications occurred. The objective response rate (ORR) was 56.1% and 87.8% based on RECIST 1.1 and mRECIST, respectively. 15 (36.6%) patients had radiological complete tumor necrosis and the disease control rate (DCR) was 100%. The pathological complete response (pCR) and major pathological response (MPR) was 13 (31.7%) and 18 (43.9%), respectively. The incidence of microvascular invasion (MVI) was 4.9% in neoadjuvant therapy patients, compared with 64.9% before propensity score matching (PSM) and 60.9% after PSM for surgery alone patients. Neoadjuvant therapy patients had a significant better prognosis than surgery alone patients (recurrence-free survival p = 0.041, overall survival p = 0.006)., Conclusions: Our preliminary results suggest the neoadjuvant D-TACE and tislelizumab therapy is safe and benefit to the pathological results and prognosis for patients with resectable or borderline resectable HCC., Competing Interests: Declaration of competing interest None., (© 2023 Published by Elsevier Ltd.)

Introduction: The phase 3 RATIONALE-303 trial (NCT03358875) investigated the efficacy and safety of tislelizumab versus docetaxel in pretreated patients with advanced NSCLC. Here, we report the efficacy and safety results and describe the exploratory biomarker analyses., Methods: A total of 805 patients aged more than or equal to 18 years with locally advanced or metastatic squamous or nonsquamous NSCLC were randomized 2:1 to intravenous tislelizumab 200 mg or docetaxel 75 mg/m 2 every 3 weeks. Co-primary end points were overall survival (OS) in the intent-to-treat (ITT) and programmed death-ligand 1 (PD-L1) tumor cell expression greater than or equal to 25% populations. The exploratory biomarker analyses included PD-L1 expression, tumor mutation burden, and gene expression profile., Results: At the prespecified interim analysis (August 10, 2020), the co-primary end point of OS in the ITT population was met, with a statistically significant and clinically meaningful improvement in OS with tislelizumab versus docetaxel (median 17.2 versus 11.9 mo, respectively; hazard ratio [HR] = 0.64, p < 0.0001). At the final analysis (July 15, 2021), the other co-primary end point of OS in the PD-L1 tumor cell greater than or equal to 25% population was further met (median 19.3 versus 11.5 mo, respectively; HR = 0.53, p < 0.0001), and OS continued to improve in the ITT population (median 16.9 versus 11.9 mo, respectively, HR = 0.66). Exploratory biomarker analyses revealed the potential association of NOTCH1-4 mutations with improved tislelizumab efficacy for both OS and progression-free survival, whereas tissue tumor mutation burden correlated with progression-free survival benefit, but not OS benefit. No new safety signals were identified., Conclusions: Tislelizumab was found to have a significantly improved and long-term clinical benefit in OS versus docetaxel in pretreated patients with advanced NSCLC, regardless of PD-L1 expression., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Tislelizumab, an anti-programmed cell death protein-1 antibody, was specifically engineered to minimize FcɣR macrophage binding to abrogate antibody-dependent phagocytosis. Compared with chemotherapy alone, tislelizumab plus chemotherapy may improve clinical outcomes in patients with advanced nonsquamous NSCLC (nsq-NSCLC)., Methods: In this open-label phase 3 trial (RATIONALE 304; NCT03663205), patients with histologically confirmed stage IIIB or IV nsq-NSCLC were randomized (2:1) to receive either arm A: tislelizumab plus platinum (carboplatin or cisplatin) and pemetrexed every 3 weeks (Q3Ws) or arm B: platinum and pemetrexed alone Q3W during induction treatment, followed by intravenous maintenance pemetrexed Q3W. The primary end point was progression-free survival (PFS) assessed by an independent review committee; clinical response and safety and tolerability were secondary end points., Results: Overall, 332 patients (n = 222 [A]; n = 110 [B]) received treatment. With a median study follow-up of 9.8 months, PFS was significantly longer with tislelizumab plus chemotherapy compared with chemotherapy alone (median PFS: 9.7 versus 7.6 mo; hazard ratio = 0.645 [95% confidence interval: 0.462-0.902], p = 0.0044). In addition, response rates were higher and response duration was longer with combination therapy versus chemotherapy alone. Hematologic adverse events (AEs) were common in both treatment arms; the most reported AEs were grades 1 to 2 in severity. The most common grade greater than or equal to 3 AEs were associated with chemotherapy and included neutropenia (44.6% [A]; 35.5% [B]) and leukopenia (21.6% [A]; 14.5% [B])., Conclusions: Addition of tislelizumab to chemotherapy resulted in significantly prolonged PFS, higher response rates, and longer response duration compared with chemotherapy alone, identifying a new potential option for first-line treatment of advanced nsq-NSCLC irrespective of disease stage., (Copyright © 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Blocking of the interaction between Programmed cell death 1 (PD-1) and its ligand PD-L1 by monoclonal antibodies has elicited unprecedented therapeutic benefits and achieved a major breakthrough in immunotherapy of multiple types of tumors. Here, we determined the crystal structure of PD-1 in complex with the Fab fragment of tislelizumab. This monoclonal antibody was approved in December 2019 by the China National Medical Product Administration for Hodgkin's lymphoma and is under multiple clinical trials in China and the US. While the three complementarity determining regions (CDRs) in the light chain are involved in the target interaction, only CDR3 within the heavy chain interacts with PD-1. Tislelizumab binds the front β-sheet of PD-1 in a very similar way as PD-L1 binds to PD-1, thereby blocking the PD-1/PD-L1 interaction with a higher affinity. A comparative analysis of PD-1 interactions with therapeutic antibodies targeting PD-1 provides a better understanding of the blockade mechanism of PD-1/PD-L1 interaction in addition to useful information for the improvement of therapeutic antibodies capable of diminishing checkpoint signaling for cancer immunotherapy., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)