ABSTRACT
Background: SARS-CoV-2 (COVID-19) elicits a T-cell antigen-mediated immune response of variable efficacy. To understand this variability, we explored transcriptomic expression of angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) and of immunoregulatory genes in normal lung tissues from patients with non-small cell lung cancer (NSCLC). Methods: This study used the transcriptomic and the clinical data for NSCLC patients generated during the CHEMORES study [n = 123 primary resected (early-stage) NSCLC] and the WINTHER clinical trial (n = 32 metastatic NSCLC). Results: We identified patient subgroups with high and low ACE2 expression (p = 1.55 × 10-19) in normal lung tissue, presumed to be at higher and lower risk, respectively, of developing severe COVID-19 should they become infected. ACE2 transcript expression in normal lung tissues (but not in tumor tissue) of patients with NSCLC was higher in individuals with more advanced disease. High-ACE2 expressors had significantly higher levels of CD8+ cytotoxic T lymphocytes and natural killer cells but with presumably impaired function by high Thymocyte Selection-Associated High Mobility Group Box Protein TOX (TOX) expression. In addition, immune checkpoint-related molecules - PD-L1, CTLA-4, PD-1, and TIGIT - are more highly expressed in normal (but not tumor) lung tissues; these molecules might dampen immune response to either viruses or cancer. Importantly, however, high inducible T-cell co-stimulator (ICOS), which can amplify immune and cytokine reactivity, significantly correlated with high ACE2 expression in univariable analysis of normal lung (but not lung tumor tissue). Conclusions: We report a normal lung immune-tolerant state that may explain a potential comorbidity risk between two diseases - NSCLC and susceptibility to COVID-19 pneumonia. Further, a NSCLC patient subgroup has normal lung tissue expressing high ACE2 and high ICOS transcripts, the latter potentially promoting a hyperimmune response, and possibly leading to severe COVID-19 pulmonary compromise.
ABSTRACT
BACKGROUND: Cancer survivors are often underprepared for what to expect post-treatment, and there are knowledge gaps regarding cancer survivors' supportive care needs in Jordan and neighboring Arab countries. This study aimed to identify gaps in supportive care needs among adult cancer survivors seen at King Hussein Cancer Center in Amman, Jordan, and explore predictors of unmet needs. METHODS: This was an observational cross-sectional study using a modified version of the Supportive Care Needs Survey 34 item short form (SCNS-SF34). RESULTS: Two hundred and forty adult cancer survivors completed the study questionnaire. The assessed needs were highest in the financial domain, including covering living expenses, managing cancer treatment adverse effects and co-morbidities. The least prevalent reported needs were in sexuality and reproductive consultations. Late-stage diagnosis was independently associated with higher physical, psychological, health system/information, financial and overall need scores, with p-values of 0.032, 0.027, 0.052, 0.002 and 0.024, respectively. The overall quality of life score was independently and inversely associated with physical, psychological, health system/information, financial and overall need domains, with p-values of 0.015, <0.0001, 0.015, 0.004 and 0.0003, respectively. CONCLUSIONS: This needs assessment identified problem areas for targeting interventions across the Jordanian cancer survivor population, and understanding these findings highlights opportunities for intervention to address gaps in care.