Spontaneous regression of metastatic renal cell carcinoma (mRCC) is a rare event, often associated with an activation of innate immunity by various triggers. SARS-CoV-2 infection induces a strong inflammatory response in some patients and a cytokine storm is one of the main causes of severe morbidity and mortality associated with the virus. Here, we describe two cases of patients with histologically and radiologically proven mRCC whose treatment was delayed due to COVID-19 and who experienced spontaneous tumour regression following the infection. Both patients reported here had predominantly pulmonary and mediastinal involvement and underwent nephrectomy. The interval between the diagnosis of COVID-19 and the detection of tumour regression was 3 and 4 months, respectively. Although approved vaccines and other measures are clearly the best way to prevent COVID-19-associated morbidity and mortality in cancer patients, we hypothesize that innate immunity activation by the infection can contribute to tumour regression in special circumstances.

Department of Oncology 1st Faculty of Medicine Charles University and Thomayer University Hospital 14059 Prague Czech Republic

Department of Radiology District Hospital Kladno 27201 Kladno Czech Republic

Department of Radiology Medicon 14000 Prague Czech Republic

Department of Radiology Thomayer University Hospital 14059 Prague Czech Republic

Department of Urology District Hospital Kladno 27201 Kladno Czech Republic

See more in PubMed

Bumpus H.C. The Apparent Disappearance of Pulmonary Metastasis in a Case of Hypernephroma Following Nephrectomy. J. Urol. 1928;20:185–192. doi: 10.1016/S0022-5347(17)73147-3. DOI

Jenkins G.D. Regression of Pulmonary Metastasis Following Nephrectomy for Hypernephroma: Eight Year Follow-up. J. Urol. 1959;82:37–40. doi: 10.1016/S0022-5347(17)65825-7. PubMed DOI

Melichar B., Vaněčková J., Morávek P., Urminská H., Podhola M. Spontaneous regression of renal cell carcinoma lung metastases in a patient with psoriasis. Acta Oncol. 2009;48:925–927. doi: 10.1080/02841860902882451. PubMed DOI

Behzad N. Immunology of the Spontaneous Remission of Cancer. Int. J. Cancer Clin. Res. 2019;6:112. doi: 10.23937/2378-3419/1410112. DOI

Challenor S., Tucker D. SARS-CoV-2-induced remission of Hodgkin lymphoma. Br. J. Haematol. 2021;192:415. doi: 10.1111/bjh.17116. PubMed DOI

Sollini M., Gelardi F., Carlo-Stella C., Chiti A. Complete remission of follicular lymphoma after SARS-CoV-2 infection: From the “flare phenomenon” to the “abscopal effect”. Eur. J. Nucl. Med. Mol. Imaging. 2021;48:2652–2654. doi: 10.1007/s00259-021-05275-6. PubMed DOI PMC

Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. doi: 10.1016/S0140-6736(20)30183-5. PubMed DOI PMC

Tay M.Z., Poh C.M., Rénia L., Macary P.A., Ng L.F.P. The trinity of COVID-19: Immunity, inflammation and intervention. Nat. Rev. Immunol. 2020;20:363–374. doi: 10.1038/s41577-020-0311-8. PubMed DOI PMC

Jordan S.C., Zakowski P., Tran H.P., Smith E.A., Gaultier C., Marks G., Zabner R., Lowenstein H., Oft J., Bluen B., et al. Compassionate Use of Tocilizumab for Treatment of SARS-CoV-2 Pneumonia. Clin. Infect. Dis. 2020;71:3168–3173. doi: 10.1093/cid/ciaa812. PubMed DOI PMC

Carvelli J., Demaria O., Vély F., Batista L., Benmansour N.C., Fares J., Carpentier S., Thibult M.-L., Morel A., Remark R., et al. Association of COVID-19 inflammation with activation of the C5a–C5aR1 axis. Nature. 2020;588:146–150. doi: 10.1038/s41586-020-2600-6. PubMed DOI PMC

Jordan S.C. Innate and adaptive immune responses to SARS-CoV-2 in humans: Relevance to acquired immunity and vaccine responses. Clin. Exp. Immunol. 2021;204:310–320. doi: 10.1111/cei.13582. PubMed DOI PMC

Law T.M., Motzer R.J., Mazumdar M., Sell K.W., Walther P., O’Connell M., Khan A., Vlamis V., Vogelzang N.J., Bajorin D.F. Phase iii randomized trial of interleukin-2 with or without lymphokine-activated killer cells in the treatment of patients with advanced renal cell carcinoma. Cancer. 1995;76:824–832. doi: 10.1002/1097-0142(19950901)76:5<824::AID-CNCR2820760517>3.0.CO;2-N. PubMed DOI

Klapper J.A., Downey S.G., Smith F.O., Yang J.C., Hughes M.S., Kammula U.S., Sherry R.M., Royal R.E., Steinberg S.M., Rosenberg S. High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma. Cancer. 2008;113:293–301. doi: 10.1002/cncr.23552. PubMed DOI PMC

Motzer R.J., Rini B.I., McDermott D.F., Frontera O.A., Hammers H.J., Carducci M.A., Salman P., Escudier B., Beuselinck B., Amin A., et al. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: Extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol. 2019;20:1370–1385. doi: 10.1016/S1470-2045(19)30413-9. PubMed DOI PMC

Haineala B., Zgura A., Diaconu C., Mehedintu C., Bacinschi X., Anghel R.M. Long-term Response After Stopping Immunotherapy in a Patient With Metastatic Renal Cancer. Vivo. 2021;35:1805–1810. doi: 10.21873/invivo.12441. PubMed DOI PMC

Campesato L.F., Weng C.-H., Merghoub T. Innate immune checkpoints for cancer immunotherapy: Expanding the scope of non T cell targets. Ann. Transl. Med. 2020;8:1031. doi: 10.21037/atm-20-1816. PubMed DOI PMC

Beberok A., Wrześniok D., Minecka A., Rok J., Delijewski M., Rzepka Z., Respondek M., Buszman E. Ciprofloxacin-mediated induction of S-phase cell cycle arrest and apoptosis in COLO829 melanoma cells. Pharmacol. Rep. 2018;70:6–13. doi: 10.1016/j.pharep.2017.07.007. PubMed DOI

Gao Y., Shang Q., Li W., Guo W., Stojadinovic A., Mannion C., Man Y.-G., Chen T. Antibiotics for cancer treatment: A double-edged sword. J. Cancer. 2020;11:5135–5149. doi: 10.7150/jca.47470. PubMed DOI PMC

Carella A.M., Beltrami G., Pica G., Carella A., Catania G. Clarithromycin potentiates tyrosine kinase inhibitor treatment in patients with resistant chronic myeloid leukemia. Leuk. Lymphoma. 2012;53:1409–1411. doi: 10.3109/10428194.2012.656105. PubMed DOI

Tsikala-Vafea M., Belani N., Vieira K., Khan H., Farmakiotis D. Use of antibiotics is associated with worse clinical outcomes in patients with cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis. Int. J. Infect. Dis. 2021;106:142–154. doi: 10.1016/j.ijid.2021.03.063. PubMed DOI