Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. // Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. // Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. // Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. // Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. // Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19–related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). // Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed

Local and systemic induction of an abundant CD4+CD25+ regulatory T cell population in non-Hodgkin's lymphoma

To investigate their importance in non-Hodgkin’s lymphoma (NHL), I enumerated Treg cells in peripheral blood mononuclear cells (PBMC) and involved tissues from 30 newly diagnosed patients CD25+FoxP3+CD127lowCD4+ Treg cells were increased markedly in PBMC (median=20.4% CD4 T cells, n=20) versus healthy controls (median=3.2%, n=13: p<0.001, rank sum test) and correlated with serum lactate dehydrogenase (n=14; Rs=0.79, p<0.001) and disease stage. I documented poor proliferation of T cells with mitogen ConA and almost none with recall antigens PPD and DPT in both PBMC and involved tissue samples (n=9). T cell hyporesponsiveness was reversed by depleting CD25+ cells (n=4), or by adding anti-CDLA-4 (n=3), supporting the view that Treg cells explain the systemic immunosuppression seen in NHL. As a high percentage of Treg cells were also present in involved tissues (patients’ involved tissues median=38.8% of CD4 T cells (n=15) vs. reactive nodes median=11.6% of CD4 T cells (n=2); p=0.02, rank sum test), I determined if tumour cells could induce a T regulatory phenotype. I incubated CD25+ depleted PBMC with tumour cells in vitro for five days. A dose and time dependent T regulatory phenotype induction from CD25+ depleted PBMC fractions were seen (n=6, maximum induction of 86.7%). Partial induction was seen when these fractions were separated with transwells. These ‘induced Treg cells’ were FACS sorted and suppressed effector T cells proliferation. I conclude that NHL cells are powerful inducers of Treg cells. These cells circulate systemically and induce active immune tolerance both systematically and within tumour microenvironment, thus representing a new therapeutic target in NHL.EThOS - Electronic Theses Online ServiceGBUnited Kingdo