Journal for immunotherapy of cancer
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J Immunother Cancer · Nov 2020
Antimetabolite pemetrexed primes a favorable tumor microenvironment for immune checkpoint blockade therapy.
The immune checkpoint blockade (ICB) targeting programmed cell death-1 (PD-1) and its ligand (PD-L1) has been proved beneficial for numerous types of cancers, including non-small-cell lung cancer (NSCLC). However, a significant number of patients with NSCLC still fail to respond to ICB due to unfavorable tumor microenvironment. To improve the efficacy, the immune-chemotherapy combination with pemetrexed, cis/carboplatin and pembrolizumab (anti-PD-1) has been recently approved as first-line treatment in advanced NSCLCs. While chemotherapeutic agents exert beneficial effects, the underlying antitumor mechanism(s) remains unclear. ⋯ Our findings reveal novel mechanisms showing that pemetrexed upregulates PD-L1 expression and primes a favorable microenvironment for ICB, which provides a mechanistic basis for the combinatory chemoimmunotherapy in NSCLC treatment.
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J Immunother Cancer · Oct 2020
Impact of COVID-19 on patients with rheumatic complications of cancer immunotherapy: results of a registry survey.
Immune checkpoint inhibitors (ICI) block negative regulatory molecules, such as CTLA-4, PD-1 and PD-L1, in order to mount an antitumor response. T cells are important for antiviral defense, but it is not known whether patients with cancer treated with ICI are more or less vulnerable to viral infections such as COVID-19. Furthermore, immunosuppressive treatment of immune-related adverse events (irAE) may also impact infection risk. ⋯ Oncologists held ICI in a quarter of the patients still on them, particularly women, those on anti-PD-(L)1 monotherapy, and those who had had a good cancer response. The incidence of COVID-19 was no higher on patients still on ICI. None of the patients on disease-modifying antirheumatic drugs or biological immunosuppressive medications developed COVID-19.
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J Immunother Cancer · Oct 2020
Infiltrating pattern and prognostic value of tertiary lymphoid structures in resected non-functional pancreatic neuroendocrine tumors.
Tertiary lymphoid structures (TLS) are associated with favorable survival and play a critical role in most solid tumors. However, investigations of TLS are lacking in patients with grade 1 or grade 2 (G1/G2) non-functional pancreatic neuroendocrine tumors (NF-PanNETs). This study aimed to investigate the presence, cellular composition, association with tumor-infiltrating immune cells, and prognostic value of TLS in G1/G2 NF-PanNETs. ⋯ The presence of TLS is an independent and favorable predictor of resected G1/G2 NF-PanNETs, which may play a role in cancer immunobiology.
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J Immunother Cancer · Oct 2020
Analysis of the molecular nature associated with microsatellite status in colon cancer identifies clinical implications for immunotherapy.
Microsatellite instability in colon cancer implies favorable therapeutic outcomes after checkpoint blockade immunotherapy. However, the molecular nature of microsatellite instability is not well elucidated. ⋯ Our analysis unraveled the difference in the molecular nature and genomic variance in MSI and MSS colon cancer. The microsatellite status-related gene signature is better at predicting the prognosis of patients with colon cancer and response to the combination of immune checkpoint inhibitor-based immunotherapy and anti-VEGF therapy.
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J Immunother Cancer · Oct 2020
Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8.
To determine safety and efficacy of single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab in stage III-IVB head and neck cancer. ⋯ Single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab is feasible and achieves a high biopsy-proven pCR rate.