Spontaneous tumor regression following COVID-19 vaccination

Abstract

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.

Keywords: COVID-19; head and neck neoplasms; immunogenicity; translational medical research; tumor microenvironment; vaccine.

Figure 1

Temporal overview of a metastatic nodule in right lower lobe at different timepoints, before and after COVID-19 vaccination with mRNA-1273. Other bilateral pulmonary metastases (not shown) have presented the same behavior overtime. (A) In July 2020, when metastasis was initially confirmed by biopsy, the nodule measured 1.4 cm. (B) In November 2020, the nodule measured 2.6 cm. (C) In February 2021, a few days after the patient received the first dose of the mRNA-1273 vaccine, the nodule measured 3.0 cm. (D) In March 2021, 1 month after the patient received the second dose of the mRNA-1273 vaccine, the nodule measured 2.5 cm. CT images acquired approximately 3 months (E), 6 months (F), and 9 months (G) after vaccination, show progressive decrease in size of the lesion, measuring 1.5 cm, 1.0 cm, and 0.8 cm, respectively. (H) The timeline at the bottom of the figure shows the timing of events. (I) Representative images demonstrating changes in tumor immune microenvironment composition of the primary parotid tumor (pre vaccine) and the lung metastasis (post vaccine; lung-met II) using imaging mass cytometry (750×750 pixels, length×width, respectively). (J) Imaging mass cytometry cell subpopulation clusters. PORT, postoperative radiation therapy; vax., vaccination.

Figure 2

Imaging mass cytometry indicates robust anti-tumor immune response following COVID-19 vaccination. (A) Clustergram of imaging mass cytometry quantification in biopsy specimens from primary tumor and prevaccination (Pre-Vax.), and postvaccination (Post-Vax.) lung metastases (Lung Met.). I and II indicate specimens from different regions taken at the same time. Color axis represents each phenotype subpopulation frequency (z-normalized density [cells/mm²] values), red for high frequency and blue for low frequency or absence (−2); (B) Percentage of proliferative (Ki67+) tumor cells (pan-CK+ and/or p63+) in Pre-Vax. and Post-Vax. lung metastasis specimens. (C) Percentage of indicated immune cell populations as percentage of total immune cells in Pre-Vax. and Post-Vax. lung metastasis specimens. (D–F) Comparison of Pre-Vax. and Post-Vax. lung metastasis specimens for (D) ratio of CD8+ T cells to regulatory T cells (Tregs), (E) percentages of CD8+ T cells and CD4+ T cells positive for TIGIT, and (F) percentages of CD8+ T cells and CD4+ T cells positive for TIM3. +, positive.