RESUMEN
Vaccination against COVID-19 is critical for immuno-compromised individuals, including patients with cancer. Systemic reactogenicity, a manifestation of the innate immune response to vaccines, occurs in up to 69% of patients following vaccination with RNA-based COVID-19 vaccines. Tumor regression can occur following an intense immune-inflammatory response and novel strategies to treat cancer rely on manipulating the host immune system. Here, we report spontaneous regression of metastatic salivary gland myoepithelial carcinoma in a patient who experienced grade 3 systemic reactogenicity, following vaccination with the mRNA-1273 COVID-19 vaccine. Histological and immunophenotypic inspection of the postvaccination lung biopsy specimens showed a massive inflammatory infiltrate with scant embedded tumor clusters (<5%). Highly multiplexed imaging mass cytometry showed that the postvaccination lung metastasis samples had remarkable immune cell infiltration, including CD4+ T cells, CD8+ T cells, natural killer cells, B cells, and dendritic cells, which contrasted with very low levels of these cells in the prevaccination primary tumor and lung metastasis samples. CT scans obtained 3, 6, and 9 months after the second vaccine dose demonstrated persistent tumor shrinkage (50%, 67%, and 73% reduction, respectively), suggesting that vaccination stimulated anticancer immunity. Insight: This case suggests that the mRNA-1273 COVID-19 vaccine stimulated anticancer immunity and tumor regression.
Asunto(s)
Vacuna nCoV-2019 mRNA-1273 , Inmunidad Innata , Inmunogenicidad Vacunal , Neoplasias Pulmonares/inmunología , Mioepitelioma/inmunología , Neoplasias de la Parótida/cirugía , Linfocitos B , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/secundario , Persona de Mediana Edad , Mioepitelioma/diagnóstico por imagen , Mioepitelioma/secundario , Neoplasias de la Parótida/patologíaRESUMEN
BACKGROUND: Protein tyrosine kinase (PTK) inhibition has been identified as a promising strategy in the development of new selective therapies, targeting the signaling pathways in melanoma progression. Gleevec, a novel class of anti-tumor drugs, may have a potential therapeutic benefit in melanoma, which involves abnormal activation of abl, c-kit, and platelet-derived growth factor (PDGF) tyrosine kinases. METHODS: Tumor biopsies from 13 patients with metastatic melanoma were screened by immunohistochemistry for PTK [c-kit, C-abl, Abl-related gene (ARG), PDGF receptor-alpha (PDGFR-alpha) and PDGFR-beta] expression before and after being treated with Gleevec @ 400 mg bid for 2 weeks. Both, percentage of positive cells and staining intensity were evaluated. RESULTS: We found a statistically significant (p < 0.01) selective loss of PTK expression in the follow-up biopsy, both in intensity and number of positive cells. PDGFR-alpha and -beta had the highest level of expression reduction. One patient had a durable clinical response, and the follow-up biopsy showed negative expression for four of the PTKs, namely c-abl, ARG, PDGFR-alpha, and beta. CONCLUSIONS: Our study reports for the first time the in vivo effect of Gleevec in the induction of apparently selective reduction of PTKs expression under anti-tyrosine kinases treatment, suggesting its potential role in melanoma treatment.