SARS-CoV-2 Infection and Vaccination, Immune Dysregulation, and Cancer Dace Pjanova, Aysha Rafeeque Vaccines, 2026 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection induces heterogeneous immune responses that influence both acute disease severity and long-term immune remodeling. A key question in the context of infection and vaccination is whether SARS-CoV-2 exerts direct oncogenic effects or instead acts as a transient immunological stressor capable of reinforcing tumor-permissive pathways. Current evidence does not support classical viral oncogenesis. Rather, severe infection is characterized by early interferon (IFN) imbalance followed by NF-κB-dominant inflammatory amplification, promoting sustained IL-6/JAK–STAT3 and MAPK signaling, chronic cytokine production, metabolic reprogramming, and impaired antitumor immune surveillance. At the molecular level, viral structural proteins modulate host signaling networks. The spike (S1) protein engages TLR2/TLR4–MyD88 pathways, activating NF-κB and MAPK cascades, while the membrane (M) protein reinforces NF-κB–STAT3 circuits linked to epithelial–mesenchymal transition and inflammatory gene expression. These mechanisms intensify pre-existing oncogenic signaling without initiating malignant transformation. Tissue-specific responses are further shaped by IFN competence, renin–angiotensin system balance, and metabolic context. In parallel, immune evasion programs shared by chronic viral infection and cancer, including checkpoint upregulation, impaired antigen presentation, and suppressive myeloid expansion, may be transiently reinforced following severe infection. In contrast, SARS-CoV-2 vaccination induces spatially restricted, self-limited innate activation without sustained inflammatory signaling or persistent antigen exposure. By preventing severe disease and chronic immune dysregulation, vaccination interrupts pathways hypothesized to intersect with cancer biology, with no evidence of increased cancer incidence. Ongoing longitudinal studies are required to clarify the long-term oncologic implications of post-infectious immune remodeling.
IgA class-switched CD27-CD21+B cells in IgA nephropathy Anna Popova, Baiba Slisere, Karlis Racenis, Viktorija Kuzema, Roberts Karklins, et al. Nephrology Dialysis Transplantation, 2025 Background Immunoglobulin A nephropathy (IgAN) is characterized by the production of galactose-deficient IgA1 (GdIgA1) antibodies. As the source of pathogenic antibodies, B cells are central to IgAN pathogenesis, but the B cell activation pathways as well as the potential B cell source of dysregulated IgA secretion remain unknown. Methods We carried out flow cytometry analysis of peripheral blood B cells in patients with IgAN and control subjects with a focus on IgA-expressing B cells to uncover the pathways of B cell activation in IgAN and how these could give rise to pathogenic GdIgA1 antibodies. Results In addition to global changes in the B cell landscape—expansion of naïve and reduction in memory B cells—IgAN patients present with an increased frequency of IgA-expressing B cells that lack the classical memory marker CD27, but are CD21+. IgAN patients furthermore have an expanded population of IgA+ antibody-secreting cells, which correlate with serum IgA levels. Both IgA+ plasmabalsts and CD27− B cells co-express GdIgA1. Implicating dysregulation at mucosal surfaces as the driver of such B cell differentiation, we found a correlation between lipopolysaccharide in the serum and IgA+CD27− B cell frequency. Conclusion We propose that dysregulated immunity in the mucosa may drive de novo B cell activation within germinal centres, giving rise to IgA+CD27− B cells and subsequently IgA-producing plasmablasts. These data integrate B cells into the paradigm of IgAN pathogenesis and allow further investigation of this pathway to uncover biomarkers and develop therapeutic interventions.
Bacteriophage–derived double-stranded rna (larifan) exerts variable effects on human blood monocytes depending on age and sex of donors R. Dovhyi, M. Rudyk, T. Serhiichuk, Yu. Yumyna, A. Dvukhriadkina, et al. Ukrainian Biochemical Journal, 2024 To date, great attention is paid to sex and age differences in the therapeutic effectiveness of drugs, including those that impact the immune system. Bacteriophage-derived dsRNA is the main component of the medicinal product Larifan, which exhibits interferonogenic activity. This study aimed to estimate the effect of Larifan on the activation status of human peripheral blood monocytes collected from donors of different ages and sex. Blood samples were obtained from the healthy volunteers, divided into 4 groups: young men and young women aged from 20 to 39 years, aged men and aged women from 54 to 69 years old. EDTA-anticoagulated blood samples were exposed to 200 μg/ml Larifan for 30 min, cells were washed and treated to study phagocytic index, ROS generation and expression of phenotypic markers. Only live monocytes selected by flow cytometry were included in the analysis. It was shown that monocytes from young as well as from aged females turned out to be quite inert to the treatment with Larifan. Monocytes from young males after the treatment demonstrated a minor decrease in phagocytic activity and significant down-regulation of ROS generation. Monocytes from aged adults showed clear sex-based differences in the basal cell phenotype. Thus, compared to monocytes from women, the monocytes from men over 50 after the treatment with Larifan showed decreased phagocytic activity and CD86 expression along with increased CD206 expression. Taken together, these results indicate the need for further studies of Larifan focused on developing personalized treatment depending on the age and sex of an individual. Keywords: double-stranded RNA, Larifan, monocytes, phagocytosis, reactive oxygen species, sex and age differences
The Price of Human Evolution: Cancer-Testis Antigens, the Decline in Male Fertility and the Increase in Cancer Jekaterina Erenpreisa, Ninel Miriam Vainshelbaum, Marija Lazovska, Roberts Karklins, Kristine Salmina, et al. International Journal of Molecular Sciences, 2023 The increasing frequency of general and particularly male cancer coupled with the reduction in male fertility seen worldwide motivated us to seek a potential evolutionary link between these two phenomena, concerning the reproductive transcriptional modules observed in cancer and the expression of cancer-testis antigens (CTA). The phylostratigraphy analysis of the human genome allowed us to link the early evolutionary origin of cancer via the reproductive life cycles of the unicellulars and early multicellulars, potentially driving soma-germ transition, female meiosis, and the parthenogenesis of polyploid giant cancer cells (PGCCs), with the expansion of the CTA multi-families, very late during their evolution. CTA adaptation was aided by retrovirus domestication in the unstable genomes of mammals, for protecting male fertility in stress conditions, particularly that of humans, as compensation for the energy consumption of a large complex brain which also exploited retrotransposition. We found that the early and late evolutionary branches of human cancer are united by the immunity-proto-placental network, which evolved in the Cambrian and shares stress regulators with the finely-tuned sex determination system. We further propose that social stress and endocrine disruption caused by environmental pollution with organic materials, which alter sex determination in male foetuses and further spermatogenesis in adults, bias the development of PGCC-parthenogenetic cancer by default.
Liver progenitor cells perform wound healing in a scratch assay by concerted bistable circuits M Lazovska, K Salmina, D Pjanova, P Zayakin, BI Gerashchenko, ... npj Systems Biology and Applications , 2026 2026
Antigen-specific B cell responses in treatment-naive and chlorambucil-treated patients with chronic lymphocytic leukemia B Šlisere, R Kārkliņš, A Plēgermane, EE Morozova, R Petrovska, ... Scientific Reports , 2026 2026
Resistance of BRAFV600E-mutant melanoma to Vemurafenib: A senescence-induced swing from differentiation to blastulation followed by proliferation F Rumnieks, NM Vainshelbaum, K Salmina, M Lazovska, M Kreismane, ... Cancer Letters, 218430 , 2026 2026 Citations: 1
SARS-CoV-2 Infection and Vaccination, Immune Dysregulation, and Cancer D Pjanova, A Rafeeque Vaccines 14 (3), 255 , 2026 2026
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Adjuvant immunotherapy in the modern management of resectable melanoma: current status and outlook to 2028 (vol 10, 104295, 2025) M Donia, H Jespersen, M Jalving, R Lee, H Eriksson, C Hoeller, ... 2026
Corrigendum to “Adjuvant immunotherapy in the modern management of resectable melanoma: current status and outlook to 2028”:[ESMO Open 10 (2025) 104295] M Donia, H Jespersen, M Jalving, R Lee, H Eriksson, C Hoeller, ... ESMO open 11 (1), 105492 , 2026 2026
The value of peritumoral lymphocyte infiltration in progression free survival in TERT and CHEK2 mutant stage I and II melanoma T Zablocka, D Pjanova, S Isajevs JOURNAL OF PATHOLOGY 267 , 2025 2025
The value of peritumoral lymphocyte infiltration in progression-free survival (PFS) of NRAS, TERT and CHEK2 mutant melanoma S Isajevs, T Zablocka, D Pjanova VIRCHOWS ARCHIV 487, S103-S103 , 2025 2025
EFFECT OF LARIFAN ON MONOCYTES OF AGED C57BL/6 AND BALB/C MICE in vitro HG Kononov, AR Dvukhriadkina, KS Ostrovska, RS Dovhyi, MP Rudyk, ... Biotechnologia Acta 18 (3), 34-38 , 2025 2025
Case reports and review of immune checkpoint inhibitor therapy and vitiligo in advanced cutaneous melanoma D Pjanova, S Donina SOUTH EAST EUROPEAN JOURNAL OF IMMUNOLOGY Учредители: Scientific Foundation … , 2025 2025
Adjuvant immunotherapy in the modern management of resectable melanoma: current status and outlook to 2028 M Donia, H Jespersen, M Jalving, R Lee, H Eriksson, C Hoeller, ... ESMO open 10 (3), 104295 , 2025 2025 Citations: 10
IgA class-switched CD27 − CD21 + B cells in IgA nephropathy A Popova, B Slisere, K Racenis, V Kuzema, R Karklins, M Saulite, J Seilis, ... Nephrology Dialysis Transplantation 40 (3), 505-515 , 2025 2025 Citations: 17
Bacteriophage derived dsRNA induces polarized activation of alveolar macrophages from Balb/c and C57Bl/6 mice in vitro in sex-and age-dependent manner R Dovhyi, A Dvukhriadkina, K Ostrovska, M Rudyk, I Verhovcova, ... Cellular Immunology 408, 104916 , 2025 2025 Citations: 1
Effect of Larifan on monocytes of aged C57BL/6 and BALB/C mice in vitro. Biotechnologia Аcta, 18 (3), 34–38 HG Kononov, AR Dvukhriadkina, KS Ostrovska, RS Dovhyi, M Rudyk, ... 2025
Telomere length in hereditary melanoma patients with variants in telomere biology related genes D Pjanova, MK Kreismane EJC Skin Cancer 3 , 2025 2025
Enhanced differentiation of IgA + class-switched CD27 - CD21 + B cells in patients with IgA nephropathy A Popova, B Slisere, K Racenis, V Kuzema, R Karklins, M Saulite, J Seilis, ... Medrxiv, 2024.04. 29.24306572 , 2024 2024 Citations: 1
Liver regeneration by oval cells employing bistability of stemness-senescence, Hippo signaling, EMT-MET, and polyploidy circuit M Lazovska, K Salmina, D Pjanova, BI Gerashchenko, J Erenpreisa BioRxiv, 2024.03. 26.586724 , 2024 2024 Citations: 1
Immunomodulatory properties of bacteriophage derived dsRNA of different size and their use as anticancer vaccine adjuvants N Dobrovolskienė, R Balevičius, A Mlynska, K Žilionytė, JA Krasko, ... Vaccine 42 (3), 512-521 , 2024 2024 Citations: 2
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Melanoma prone families with CDK4 germline mutation: phenotypic profile and associations with MC1R variants HE Puntervoll, XR Yang, HH Vetti, IM Bachmann, MF Avril, M Benfodda, ... Journal of medical genetics 50 (4), 264-270 , 2013 2013 Citations: 204
Predictors of sun protection behaviors and severe sunburn in an international online study R Bränström, NA Kasparian, Y Chang, P Affleck, A Tibben, LG Aspinwall, ... Cancer Epidemiology, Biomarkers & Prevention 19 (9), 2199-2210 , 2010 2010 Citations: 155
Toluidine blue test for sperm DNA integrity and elaboration of image cytometry algorithm J Erenpreisa, J Erenpreiss, T Freivalds, M Slaidina, R Krampe, J Butikova, ... Cytometry Part A: The Journal of the International Society for Analytical … , 2003 2003 Citations: 147
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CDKN2A and CDK4 variants in Latvian melanoma patients: analysis of a clinic-based population D Pjanova, L Engele, JA Randerson-Moor, M Harland, DT Bishop, ... Melanoma research 17 (3), 185-191 , 2007 2007 Citations: 48
Skin examination behavior: the role of melanoma history, skin type, psychosocial factors, and region of residence in determining clinical and self-conducted skin examination NA Kasparian, R Bränström, Y Chang, P Affleck, LG Aspinwall, A Tibben, ... Archives of dermatology 148 (10), 1142-1151 , 2012 2012 Citations: 44
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Oncolytic viruses sensitize human tumor cells for NY-ESO-1 tumor antigen recognition by CD4+ effector T cells. T Delaunay, M Violland, N Boisgerault, S Dutoit, V Vignard, C Münz, ... Oncoimmunology 7 (3), e1407897 , 2018 2018 Citations: 36
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Effects of BRAF V600E and NRAS mutational status on the progression-free survival and clinicopathological characteristics of patients with melanoma T Zablocka, M Kreismane, D Pjanova, S Isajevs Oncology Letters 25 (1), 27 , 2022 2022 Citations: 33
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Somatic BRAF and NRAS mutations in familial melanomas with known germline CDKN2A status: a GenoMEL study A Zebary, K Omholt, R Van Doorn, P Ghiorzo, K Harbst, CH Johansson, ... Journal of Investigative Dermatology 134 (1), 287-290 , 2014 2014 Citations: 26
Germline variation at CDKN2A and associations with nevus phenotypes among members of melanoma families NJ Taylor, N Mitra, AM Goldstein, MA Tucker, MF Avril, E Azizi, ... Journal of Investigative Dermatology 137 (12), 2606-2612 , 2017 2017 Citations: 25
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Analysis of Latvian familial melanoma patients shows novel variants in the noncoding regions of CDKN2A and that the CDK4 mutation R24H is a founder mutation R Veinalde, A Ozola, K Azarjana, A Molven, LA Akslen, S Donina, ... Melanoma Research 23 (3), 221-226 , 2013 2013 Citations: 22
