Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination.

While macrophage phagocytosis is an immune defense mechanism against invading cellular organisms, cancer cells expressing the CD47 ligand send forward signals to repel this engulfment. Here we report that the reverse signaling using CD47 as a receptor additionally enhances a pro-survival function of prostate cancer cells under phagocytic attack. Although low CD47-expressing cancer cells still allow phagocytosis, the reverse signaling delays the process, leading to incomplete digestion of the entrapped cells and subsequent tumor hybrid cell (THC) formation. Viable THCs acquire c-Myc from parental cancer cells to upregulate both M1- and M2-like macrophage polarization genes. Consequently, THCs imitating dual macrophage features can confound immunosurveillance, gaining survival advantage in the host. Furthermore, these cells intrinsically express low levels of androgen receptor and its targets, resembling an adenocarcinoma-immune subtype of metastatic castration-resistant prostate cancer. Therefore, phagocytosis-generated THCs may represent a potential target for treating the disease.

Hypermetabolic lymphadenopathy following the administration of COVID-19 vaccine and immunotherapy in a lung cancer patient: a case report.

BACKGROUND: Given the current climate of the pandemic, lung cancer patients are especially vulnerable to complications from severe acute respiratory syndrome coronavirus 2 infection. As a high-risk population group, these patients are strongly advised to receive coronavirus disease 2019 vaccination in accordance with Center for Disease Control and Prevention guidelines to minimize morbidity and mortality. In recent years, immunotherapy has taken a preeminent role in the treatment of non-small cell lung cancer with dramatic improvement in overall survival. Reactive lymphadenopathy following the administration of a coronavirus disease 2019 vaccination can confound the radiographic interpretation of positron emission tomography-computed tomography or computed tomography scans from lung cancer patients receiving immunotherapy. CASE PRESENTATION: Here, we present a case of a 61-year-old Caucasian female and former smoker who developed cervical, hilar, supraclavicular, mediastinal, and left retroauricular lymphadenopathy following her coronavirus disease 2019 booster vaccination. At the time, she had been receiving long-term immunotherapy for the treatment of advanced lung adenocarcinoma. Biopsy was pursued owing to concerns of treatment failure and confirmed recurrent malignancy. CONCLUSION: This case report highlights the importance of lymph node biopsies in lung cancer patients who present with contralateral lymphadenopathy following coronavirus disease 2019 vaccination to rule out tumor recurrence in this deserving patient population.