AARS1-mediated lactylation reprograms macrophage lipid metabolism to restrict antitumor immunity

Background
Tumor-derived lactate has long been regarded as a metabolic waste product. However, accumulating evidence indicates that lactate also functions as a signaling molecule that actively remodels the tumor immune microenvironment. How lactate-dr…

DNA hypomethylation identifying clinical benefit subgroup of small-cell lung cancer: multi-omics analysis of a phase II trial with durvalumab plus olaparib as maintenance therapy

Background
Long-term survival of extensive-stage small-cell lung cancer (ES-SCLC) remains rare, with most patients experiencing disease progression during maintenance therapy. Poly (ADP-ribose) polymerase (PARP) inhibitors have the potential to confer…

Phase I safety, efficacy, and biomarker response evaluations of three oral PD-L1 inhibitors: INCB086550, INCB099280, and INCB099318

Background
Orally administered small-molecule programmed death ligand 1 (PD-L1) inhibitors may have the potential to improve patient outcomes in the treatment of a range of cancers compared with their antibody-based counterparts. A small molecule migh…

Impact on survival of severe immuno-related adverse events in deficient mismatch repair/microsatellite instable-high digestive cancers treated with immunotherapy

Background
Deficient DNA mismatch repair/microsatellite instability-high (dMMR/MSI-H) cancers are very sensitive to immune checkpoint inhibitors (ICIs), yet their use is frequently complicated by immune-related adverse events (irAEs). Our study analyz…

Durable responses to triplet immunotherapy targeting TGF-{beta}, PD-L1, and tumor antigen, with an IL-15 receptor superagonist in mismatch repair proficient castration-resistant prostate cancer

Background
Immune checkpoint blockade is minimally active in unselected castration-resistant prostate cancer (CRPC) and does not reproducibly yield durable decreases in prostate-specific antigen (PSA) levels.

Methods
The Quick Efficacy Seeking Trial …

Induction toripalimab plus chemotherapy sequential concurrent chemoradiotherapy with nimotuzumab followed by toripalimab maintenance in stage IVB hypopharyngeal squamous cell carcinoma: a single-arm phase 2 study

Background
Optimal induction chemoimmunotherapy sequential concurrent chemoradiotherapy (cCRT) in locally advanced hypopharyngeal squamous cell carcinoma (HSCC) remains undefined. This study aimed to evaluate toripalimab plus chemotherapy sequential c…

Personalized tumor-loaded monocyte-derived dendritic cell vaccination in combination with atezolizumab as maintenance treatment in extensive-stage small cell lung cancer (ES-SCLC): phase Ib-II VENEZOLUNG trial

Background
Despite the incorporation of atezolizumab, an anti-programmed death-ligand 1 (PD-L1) antibody, into first-line chemotherapy regimen, survival in patients with extensive-stage small cell lung cancer (ES-SCLC) remains poor. Given the role of …

Randomized phase II trial of nivolumab and ipilimumab with or without stereotactic body radiation therapy in patients with metastatic castration-resistant prostate cancer: the CheckPRO, CA209-8TY trial

Background
Metastatic castration-resistant prostate cancer (mCRPC) is among the leading causes of cancer-related mortality in men worldwide. Treatment options for mCRPC typically include chemotherapy and androgen receptor pathway inhibitors. Immune ch…

Frontline immunotherapy with response-guided subsequent treatment (FIRST) in cutaneous squamous cell carcinoma: a Bayesian causal analysis of dose intensity, early benefit, and treatment de-escalation

Background
Programmed death receptor 1 (PD-1) blockade produces high response rates in resectable and locally advanced cutaneous squamous cell carcinoma (CSCC), but how many doses are needed and whether surgery or radiation after immunotherapy (consol…

Safety and efficacy of fecal microbiota transplantation in solid cancers resistant to immune checkpoint inhibitors: results of the MITRIC trial

Background
Fecal microbiota transplantation (FMT) has shown promise in overcoming resistance to immune checkpoint inhibitors (ICIs) in early-phase cancer trials. We investigated the safety, feasibility and efficacy of FMT from ICI responders to patien…

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