Immune checkpoint blockade has vastly changed the landscape of cancer treatment and showed a promising prognosis for cancer patients. However, there is still a large portion of patients who have no response to this therapy. Therefore, it's essential to investigate biomarkers to predict the efficacy of immune checkpoint inhibitors. This article summarizes the predictive value of established biomarkers, including programmed cell death ligand 1(PD-L1) expression level, tumor mutational burden, tumor-infiltrating lymphocytes, and mismatch repair deficiency. It also addresses the predictive value of tumorous mutations, circulation factors, immune-related factors, and gut microbiome with immunotherapy treatment. Furthermore, some of the emerging novel biomarkers, and potential markers for hyper progressive disease are discussed, which should be validated in clinical trials in the future.
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http://dx.doi.org/10.7150/jca.65012 | DOI Listing |
Sci Rep
December 2024
Medical Image Analysis, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Immune checkpoint inhibitor (ICI) treatment has proven successful for advanced melanoma, but is associated with potentially severe toxicity and high costs. Accurate biomarkers for response are lacking. The present work is the first to investigate the value of deep learning on CT imaging of metastatic lesions for predicting ICI treatment outcomes in advanced melanoma.
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December 2024
Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.
Immune checkpoint inhibitors (ICI) represent new anticancer agents and have been used worldwide. However, ICI can potentially induce life-threatening severe cutaneous adverse reaction (SCAR), such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hindering continuous ICI therapy. We examine 6 cohorts including 25 ICI-induced SJS/TEN patients and conduct single-cell RNA sequencing (scRNA-seq) analysis, which shows overexpression of macrophage-derived CXCL10 that recruits CXCR3 cytotoxic T lymphocytes (CTL) in blister cells from ICI-SJS/TEN skin lesions.
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December 2024
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4 T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL.
View Article and Find Full Text PDFHere we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.
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December 2024
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Glioblastoma is immunologically "cold" and resistant to single-agent immune-checkpoint inhibitors (ICI). Our previous study of neoadjuvant pembrolizumab in surgically-accessible recurrent glioblastoma identified a molecular signature of response to ICI and suggested that neoadjuvant pembrolizumab may improve survival. To increase the power of this observation, we enrolled an additional 25 patients with a primary endpoint of evaluating the cell cycle gene signature associated with neoadjuvant pembrolizumab and performed bulk-RNA seq on resected tumor tissue (NCT02852655).
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