Targeting SPP1+TAMs associated with liver metastasis reverses immunosuppression and synergizes with immunotherapy in colorectal cancer

Background
Tumor-associated macrophages (TAMs) are critically involved in colorectal cancer (CRC) progression, yet their spatial and metabolic heterogeneity across primary and metastatic microenvironments remains poorly defined, limiting therapeutic d…

Phase II study of olaparib and durvalumab in patients with metastatic castration-resistant prostate cancer

Background
Poly(ADP-ribose) polymerase (PARP) inhibition (PARPi) is a precision medicine strategy in advanced prostate cancer, with the greatest benefit seen in a subset of patients with homologous recombination repair (HRR) gene alterations. Combinat…

Fecal microbiota transplantation combined with anti-PD-1 therapy in refractory microsatellite-stable gastric cancer: a phase I feasibility and safety study

Background
The discovery and therapeutic application of immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes in cancer treatment. However, the response rate is still low in gastrointestinal (GI) cancers. The gut microbiome…

Phase Ib multicenter study of anti-TIM-3 (S095018/Sym023) in combination with anti-PD-1 (Sym021) in patients with advanced/metastatic recurrent biliary tract cancer

Background
T-cell immunoglobulin and mucin-domain containing 3 (TIM-3) is an inhibitory receptor linked to decreased antitumor activity of immune cells. S095018 is a human anti-TIM-3 IgG2 antibody that blocks the binding of phosphatidyl serine to TIM-…

Evaluation of mixed response in tumor size and survival in patients with rare cancers treated with dual checkpoint inhibitor therapy (DART SWOG S1609)

Background
Mixed response, where different lesions within the same patient show discordant responses to treatment, remains poorly understood. To better understand the complex effects of mixed response on patient survival, we devised three different de…

First-in-human phase 1 study of RO7119929, an oral TLR7 agonist prodrug, in patients with advanced primary or metastatic liver cancers

Background
The orally available toll-like receptor 7 (TLR7) agonist prodrug RO7119929 is converted to active drug predominantly in the liver, where it is hypothesized to reprogram the local immune microenvironment. We aimed to explore the safety, phar…

Prospective study of patients with immune checkpoint inhibitor-induced hepatitis; characterization of liver injury, outcome of therapy, and management of steroid-unresponsive and steroid-dependent hepatitis

Background
Immune-related hepatitis (ir-hepatitis) ranks among the most frequent adverse events of immune checkpoint inhibitors (ICIs). Limited knowledge exists regarding the incidence, characteristics, and treatment of patients having an inadequate r…

Resistance to anti-PD-1 immunotherapy for stage III and IV melanoma: a global chart review study

Background
Anti-programmed cell death protein 1 (PD-1) immunotherapy has revolutionized the treatment of stage III and IV melanoma. Real-world data on its resistance is needed to facilitate the development of combinatorial approaches to overcome anti-…

Androgen deprivation, androgen receptor-targeted vaccination, and nivolumab in patients with high-risk localized prostate cancer

Background
In murine studies, we demonstrated that a DNA vaccine encoding the androgen receptor (pTVG-AR) given prior to androgen deprivation elicited prostate tumor-infiltrating lymphocytes and an antitumor response. The current trial evaluated this …

Influence of body composition on the efficacy of nivolumab plus ipilimumab for metastatic clear cell renal cell carcinoma

Background
Immune checkpoint inhibitor therapy (ICI) with nivolumab+ipilimumab is a first-line (1L) standard for metastatic clear cell renal cell carcinoma (ccRCC), yet outcomes remain heterogeneous. Increasing evidence suggests that host factors infl…

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