Background: Since the beginning of the SARS-Cov2 pandemic, cancer patients affected by COVID-19 have been reported to experience poor prognosis; however, a detailed quantification of the effect of cancer on outcome of unvaccinated COVID-19 patients has not been performed.
Methods: To carry out a systematic review of the studies comparing the outcome of unvaccinated COVID-19 patients with and without cancer, a search string was devised which was used to identify relevant publications in PubMed up to December 31, 2020. We selected three outcomes: mortality, access to ICU, and COVID-19 severity or hospitalization. We considered results for all cancers combined as well as for specific cancers. We conducted random-effects meta-analyses of the results, overall and after stratification by region. We also performed sensitivity analyses according to quality score and assessed publication bias.
Results: For all cancer combined, the pooled odds ratio (OR) for mortality was 2.32 (95% confidence interval [CI] 1.82-2.94, I2 for heterogeneity 90.1%, 24 studies), that for ICU admission was 2.39 (95% CI 1.90-3.02, I20.0%, 5 studies), that for disease severity or hospitalization was 2.08 (95% CI 1.60-2.72, I2 92.1%, 15 studies). The pooled mortality OR for hematologic neoplasms was 2.14 (95% CI 1.87-2.44, I2 20.8%,8 studies). Data were insufficient to perform a meta-analysis for other cancers. In the mortality meta-analysis for all cancers, the pooled OR was higher for studies conducted in Asia than studies conducted in Europe or North America. There was no evidence of publication bias.
Conclusions: Our meta-analysis indicates a two-fold increased risk of adverse outcomes (mortality, ICU admission and severity of COVID-19) in unvaccinated COVID-19 patients with cancer compared to COVID-19 patients without cancer. These results should be compared with studies conducted in vaccinated patients; nonetheless, they argue for special effort to prevent SARS-Cov2 infection in patients with cancer.
Funding: No external funding was obtained.
All data generated or analysed during this study are included in the manuscript and supporting file.Dataset has been deposited on Dryad (doi:10.5061/dryad.00000004q)
Data from: Effect of SARS-CoV-2 infection on outcome of cancer patients: A systematic review and meta-analysis of studies of unvaccinated patientsDryad Digital Repository, doi:10.5061/dryad.00000004q.
The authors declare that there was no funding for this work.
Human subjects: a) All methods were carried out in accordance with relevant guidelines and regulations.b) The study was considered exempt and the informed consent was not deemed necessary given the nature of the study
- Nicolas Schlecht, Roswell Park Comprehensive Cancer Center, United States
© 2022, Di Felice et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Identification oncogenes is fundamental to revealing the molecular basis of cancer. Here, we found that FOXP2 is overexpressed in human prostate cancer cells and prostate tumors, but its expression is absent in normal prostate epithelial cells and low in benign prostatic hyperplasia. FOXP2 is a FOX transcription factor family member and tightly associated with vocal development. To date, little is known regarding the link of FOXP2 to prostate cancer. We observed that high FOXP2 expression and frequent amplification are significantly associated with high Gleason score. Ectopic expression of FOXP2 induces malignant transformation of mouse NIH3T3 fibroblasts and human prostate epithelial cell RWPE-1. Conversely, FOXP2 knockdown suppresses the proliferation of prostate cancer cells. Transgenic overexpression of FOXP2 in the mouse prostate causes prostatic intraepithelial neoplasia. Overexpression of FOXP2 aberrantly activates oncogenic MET signaling and inhibition of MET signaling effectively reverts the FOXP2-induced oncogenic phenotype. CUT&Tag assay identified FOXP2-binding sites located in MET and its associated gene HGF. Additionally, the novel recurrent FOXP2-CPED1 fusion identified in prostate tumors results in high expression of truncated FOXP2, which exhibit a similar capacity for malignant transformation. Together, our data indicate that FOXP2 is involved in tumorigenicity of prostate.
Cytotoxic CD8+ T lymphocytes (CTLs) are key players of adaptive anti-tumor immunity based on their ability to specifically recognize and destroy tumor cells. Many cancer immunotherapies rely on unleashing CTL function. However, tumors can evade killing through strategies which are not yet fully elucidated. To provide deeper insight into tumor evasion mechanisms in an antigen-dependent manner, we established a human co-culture system composed of tumor and primary immune cells. Using this system, we systematically investigated intrinsic regulators of tumor resistance by conducting a complementary CRISPR screen approach. By harnessing CRISPR activation (CRISPRa) and CRISPR knockout (KO) technology in parallel, we investigated gene gain-of-function as well as loss-of-function across genes with annotated function in a colon carcinoma cell line. CRISPRa and CRISPR KO screens uncovered 187 and 704 hits respectively, with 60 gene hits overlapping between both. These data confirmed the role of interferon‑γ (IFN-γ), tumor necrosis factor α (TNF-α) and autophagy pathways and uncovered novel genes implicated in tumor resistance to killing. Notably, we discovered that ILKAP encoding the integrin-linked kinase-associated serine/threonine phosphatase 2C, a gene previously unknown to play a role in antigen specific CTL-mediated killing, mediate tumor resistance independently from regulating antigen presentation, IFN-γ or TNF-α responsiveness. Moreover, our work describes the contrasting role of soluble and membrane-bound ICAM-1 in regulating tumor cell killing. The deficiency of membrane-bound ICAM-1 (mICAM-1) or the overexpression of soluble ICAM-1 (sICAM-1) induced resistance to CTL killing, whereas PD-L1 overexpression had no impact. These results highlight the essential role of ICAM-1 at the immunological synapse between tumor and CTL and the antagonist function of sICAM-1.