Survivor guilt: The secret burden of lung cancer survivorship.

Objectives: Historically, long-term survival following diagnosis of lung cancer has been a rare occurrence. An overall poor prognosis and the low likelihood of long-term survival are thought to precipitate survivors experiencing what is referred to as survivor guilt. This study explored the prevalence and nature of survivor guilt among lung cancer survivors. Methods: Lung cancer survivors (n = 108) completed an online survey through a national organization's online community platform. This survey included a commonly used measure of survivor guilt targeting lung cancer and a single item that asked about whether they had experienced survivor guilt associated with lung cancer. Additionally, survivors were asked to provide open-ended descriptions of survivor guilt. In-depth thematic analysis was used to analyze these in-depth responses from those with the highest guilt scores on the survey measure (top quartile). Results: Survey responses revealed a majority of study respondents endorsed survivor guilt with 55% reporting an experience of survivor guilt associated with lung cancer. In addition, 63.9% of respondents scored above the mean on the survivor guilt scale. Qualitative analysis revealed five recurring themes among respondents with the highest survivor guilt scores (top quartile): 1) mentioning the death of others, 2) questioning "why not me?" 3) the role of the passage of time on emotions experienced, 4) the role of demographic and clinical characteristics' on survivor guilt, and 5) strategies for coping with survivor guilt. Conclusions: This study identifies survivor guilt in lung cancer survivors and raises clinical awareness that managing survivor guilt is a psychosocial challenge for lung cancer survivors. Results highlight the need for addressing this critical issue.

CD8+ T cells contribute to survival in patients with COVID-19 and hematologic cancer.

Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients with cancer who were hospitalized for COVID-19, patients with hematologic cancer had higher mortality relative to patients with solid cancer. In two additional cohorts, flow cytometric and serologic analyses demonstrated that patients with solid cancer and patients without cancer had a similar immune phenotype during acute COVID-19, whereas patients with hematologic cancer had impairment of B cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses. Despite the impaired humoral immunity and high mortality in patients with hematologic cancer who also have COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Furthermore, 77% of patients with hematologic cancer had detectable SARS-CoV-2-specific T cell responses. Thus, CD8 T cells might influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in patients with hematologic cancer even in the setting of limited humoral responses.

CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer.

Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19), but the underlying immune mechanisms are unknown. In a cohort of 100 cancer patients hospitalized for COVID-19 at the University of Pennsylvania Health System, we found that patients with hematologic cancers had a significantly higher mortality relative to patients with solid cancers after accounting for confounders including ECOG performance status and active cancer status. We performed flow cytometric and serologic analyses of 106 cancer patients and 113 non-cancer controls from two additional cohorts at Penn and Memorial Sloan Kettering Cancer Center. Patients with solid cancers exhibited an immune phenotype similar to non-cancer patients during acute COVID-19 whereas patients with hematologic cancers had significant impairment of B cells and SARS-CoV-2-specific antibody responses. High dimensional analysis of flow cytometric data revealed 5 distinct immune phenotypes. An immune phenotype characterized by CD8 T cell depletion was associated with a high viral load and the highest mortality of 71%, among all cancer patients. In contrast, despite impaired B cell responses, patients with hematologic cancers and preserved CD8 T cells had a lower viral load and mortality. These data highlight the importance of CD8 T cells in acute COVID-19, particularly in the setting of impaired humoral immunity. Further, depletion of B cells with anti-CD20 therapy resulted in almost complete abrogation of SARS-CoV-2-specific IgG and IgM antibodies, but was not associated with increased mortality compared to other hematologic cancers, when adequate CD8 T cells were present. Finally, higher CD8 T cell counts were associated with improved overall survival in patients with hematologic cancers. Thus, CD8 T cells likely compensate for deficient humoral immunity and influence clinical recovery of COVID-19. These observations have important implications for cancer and COVID-19-directed treatments, immunosuppressive therapies, and for understanding the role of B and T cells in acute COVID-19.