Dr. Patrick Soon-Shiong, a billionaire surgeon and immunotherapy pioneer, has ignited a provocative debate: cancer is not the primary disease but a symptom of a collapsed immune system, with low Absolute Lymphocyte Count (ALC) as a critical indicator. Speaking to Megyn Kelly in 2025, he argued that lymphopenia, an ALC below 1,000 cells per microlitre, leaves the body defenceless against infection, cancer growth, and metastasis. Backed by decades of research and his own FDA-approved therapy, ANKTIVA (N-803), Soon-Shiong claims that restoring lymphocytes, natural killer (NK) cells and T cells, offers a paradigm shift from targeting tumours to treating the host's immune system. Is he onto something worth investigating, or is this a bold overstatement? I will examine the evidence, potential, and risks of his hypothesis, questioning the sacred cow of tumour-centric cancer treatment.
Soon-Shiong's claim hinges on ALC, a measure of lymphocytes (NK cells, CD4+ T cells, and CD8+ T cells) in the blood, as a prognostic biomarker. Studies since the 1990s, including Lymphopenia in Cancer Patients (2019), confirm that lymphopenia is a powerful predictor of poor outcomes across cancers like breast, lung, and pancreatic. Patients with ALC below 1,000 face higher risks of relapse (1.35–3.81 relative risk) and reduced survival (1.25–7.70 hazard ratio). A 2020 study in PLoS One found that low ALC correlates with increased toxicity from chemotherapy and worse survival in metastatic solid tumours.
The mechanism is straightforward: lymphocytes are the immune system's frontline soldiers. NK cells target cancer cells directly, while T cells (CD8+ cytotoxic and CD4+ helper) orchestrate immune responses and form memory cells for long-term protection. Chemotherapy and radiation, standard treatments, often induce lymphopenia by destroying these cells, paradoxically weakening the body's ability to fight cancer. Soon-Shiong argues this is why outcomes remain poor: the medical establishment has focused on killing tumours while ignoring the immune system's collapse.
His solution, ANKTIVA, an IL-15 superagonist, is the first FDA-approved therapy (2024) designed to reverse lymphopenia by proliferating NK and T cells without upregulating immunosuppressive T-regulatory cells. In the QUILT-88 trial for advanced pancreatic cancer, patients with ALC above 1,045 cells/μL and lower CA19-9 levels had a median overall survival of 7.1 months, compared to 3.1 months for those with lower ALC, a statistically significant improvement (HR 3.6, p < 0.001). The 2025 RMAT designation for ANKTIVA and PD-L1 t-haNK (engineered NK cells) further validates its potential to address lymphopenia across tumour types.
Soon-Shiong's hypothesis is compelling for several reasons. First, it aligns with the growing recognition of immunotherapy's role in cancer care. Checkpoint inhibitors like pembrolizumab rely on existing T cells, but their efficacy wanes in lymphopenic patients, as no T cells exist to activate. ANKTIVA's ability to restore lymphocyte counts could enhance these therapies, as seen in bladder cancer, where it achieved a 71% complete remission rate in BCG-unresponsive cases. Second, the focus on ALC as a biomarker is practical: it's a simple, cost-effective measure from a complete blood count (CBC), overlooked because, as Soon-Shiong notes, no therapy existed to address lymphopenia until ANKTIVA.
The potential applications are vast. If lymphopenia is a root cause, restoring ALC could not only treat cancer but prevent it in high-risk groups, like those with Lynch syndrome, through cancer vaccines. The energy efficiency of biological systems also suggests a synergy: just as organoids outperform silicon chips, biological immunotherapies may outstrip traditional drugs in efficacy and sustainability.
Yet, Soon-Shiong's hypothesis isn't without risks. Overemphasizing immune restoration could oversimplify cancer's complexity. Tumours employ multiple evasion tactics, downregulating MHC-I receptors, secreting immunosuppressive cytokines, that immunotherapy alone may not overcome. Some cancers resist NK cell attacks due to microenvironment barriers, requiring combined approaches. Focusing solely on ALC might neglect other biomarkers, like neutrophil-to-lymphocyte ratio (NLR), which also predicts outcomes.
Practical challenges include ANKTIVA's side effects, 95% of QUILT-88 patients experienced grade 3 or higher toxicities, largely from chemotherapy components, and its high cost, limiting accessibility. Ethical concerns arise with expanded access programs for ANKTIVA and PD-L1 t-haNK, as informed consent and long-term effects remain understudied. Critics on X, like @VigilantFox (August 21, 2025), praise Soon-Shiong's vision but warn of overhyping immunotherapy without addressing systemic healthcare barriers.
The sacred cow here is tumour-centric oncology, which Soon-Shiong challenges by advocating host-centric treatment. Soon-Shiong's hypothesis merits rigorous investigation. Clinical trials should expand to test ANKTIVA across diverse cancers, correlating ALC restoration with survival outcomes. Studies like QUILT-88 show promise, but larger, randomised trials are needed to confirm efficacy and safety. Integrating ALC monitoring into standard care, as Soon-Shiong suggests, could transform oncology, making it as routine as checking blood pressure.
Dr. Patrick Soon-Shiong's claim that cancer stems from immune collapse, with ALC as a key marker, is a hypothesis worth investigating. Supported by decades of data and his own FDA-approved therapy, it challenges the sacred cow of tumour-centric treatment, offering a host-focused paradigm that could prevent and treat cancer more effectively. Yet, risks like oversimplification, toxicity, and accessibility demand caution. By pairing rigorous research with open debate, we can determine if Soon-Shiong's vision is a game-changer.
https://www.vigilantfox.com/p/doctor-reveals-why-conventional-cancer