From last‑chance therapy to cancer boosters: A 2050 vision of immunoprevention in high‑risk populations

Imagine attending a hospital day‑care unit not because you are ill, but for a scheduled “cancer immune booster” every few years, like renewing a vaccine. You feel well, but a BRCA1 mutation, Lynch syndrome, or high genomic risk marks you as high risk. Rather than waiting for a tumour, your oncologist boosts your immune system to detect and eliminate abnormal cells before they become malignant—cancer interception, immunotherapy as prophylaxis.

We already have proof‑of‑principle for preventive oncology. In the UK, women at moderate or high familial risk of breast cancer are offered tamoxifen after IBIS I showed that five years of treatment reduced overall breast cancers from 9.8% to 7% at 16 years (hazard ratio 0.71).¹ Health systems already recommend tamoxifen or raloxifene for selected high‑risk women, showing society accepts systemic drugs in ostensibly healthy people when absolute benefit is compelling.² Immunoprevention by 2050 extends this logic, replacing long‑term endocrine blockade with intermittent immune education against precancerous cells or risk‑specific antigens, aiming for more precise prevention and less off‑target toxicity.

Current immunotherapies already demonstrate that the immune system can act as a patient‑specific drug factory. In melanoma, lung, bladder, kidney and haematological cancers, checkpoint inhibitors and CAR-T cells are standard of care.³  The next step is to move these agents upstream, from rescuing late‑stage disease to clearing precancerous lesions and high‑risk fields.^4,5 Topical immunotherapy in the skin offers an early example. In a randomised trial, a four‑day course of calcipotriol plus 5‑fluorouracil on sun‑exposed skin achieved an ≈88% mean reduction in facial actinic keratoses versus 26% with 5‑fluorouracil alone, with complete clearance in 27% versus 0% of patients.^6,7 Over three years, this short course cleared lesions, induced thymic stromal lymphopoietin, activated CD4⁺ and tissue‑resident memory T-cells, and reduced SCC (2/30 vs 11/40)⁷, a topical immunoprevention mirroring tamoxifen’s goal but acting via durable local immune memory.¹

Viral cancer vaccines already demonstrate immunoprevention at scale. Universal hepatitis B vaccination cut HCC in young adults from 0.4% to 0.1%⁸, and HPV vaccination yields similar gains for cervical cancer. Prophylactic HPV vaccines maintain >90% efficacy against HPV‑16/18 infection and high‑grade CIN in HPV‑naïve girls⁹, intercepting precancerous lesions.¹⁰ In England, vaccination at 12–13 yields 83.9–87.0% lower cervical cancer and 94.3–97.0% lower CIN3¹¹, and high‑coverage programmes in Sweden¹² and Australia show incidence nearing the WHO elimination threshold.¹³

By 2050, these strands could converge into routine, risk‑stratified “cancer boosters”. Instead of a five‑year tamoxifen course for someone with ≈30% lifetime breast cancer risk¹, she might receive periodic mRNA “mini‑boosters” encoding shared oncogenic antigens (e.g., HER2 or hTERT) to seed long‑lived tissue‑resident memory T-cells in the breast.¹⁴  This builds on current platforms: personalised mRNA vaccines already improve recurrence‑free survival in resected melanoma¹⁵, KRAS‑targeted vaccines induce T‑cell responses in pancreatic¹⁶ and colorectal cancer¹⁷, and Lynch syndrome carriers are receiving Nous‑209^18,19, a viral‑vector vaccine encoding shared frameshift neoantigens, with early data suggesting safety and broad immunogenicity.¹⁸ Together, these approaches move chemoprevention into the immune era, using risk‑adapted, well‑tolerated boosters to maximise benefit in people who remain well.

References

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2. National Institute for Health and Care Excellence. Familial breast cancer (breast cancer in the family). Updated 22 March 2017 ed. United Kingdom: NICE; 2013. p. 1-21.
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15. Weber JS, Carlino MS, Khattak A, et al. Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study. Lancet 2024; 403(10427): 632-44.
16. Rojas LA, Sethna Z, Soares KC, et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature 2023; 618(7963): 144-50.
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19. D’Alise AM, Willis J, Hall M, et al. 1336 Final Ph1b/2 results for nous-209 monotherapy in lynch syndrome carriers: annual revaccination boosts T cell immunity informing future cancer interception strategies. Journal for ImmunoTherapy of Cancer 2025; 13(Suppl 3).

About the author

Muhammad Habiburrahman is a PhD student in the Translational Epigenomics Group at the Institute of Reproductive and Developmental Biology (IRDB), Department of Surgery and Cancer, Imperial College London. He holds a Bachelor’s degree and a Doctor of Medicine from the University of Indonesia, and completed a clinical research fellowship at Dr. Cipto Mangunkusumo National Referral Hospital, one of Indonesia’s leading centres for cancer care and research. His current research focuses on the clinical validation of a blood-based DNA methylation biomarker to predict treatment response in relapsed ovarian cancer, with the aim of supporting its implementation in clinical practice and improving patient stratification in precision oncology. More broadly, his work explores biomarker-informed approaches to improve clinical decision-making in cancer care. His additional research interests include cancer clinical epidemiology, including trend analysis, translational multi-omics, and non-invasive biomarker development, which have further strengthened his interest in preventive oncology, particularly in relation to primary and secondary prevention strategies. He has authored more than 50 peer-reviewed publications and is actively involved in international research collaborations.

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