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Immunotherapy reprograms the patient's own immune system so that it recognizes and destroys tumor cells. The main modalities are: immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, anti-CTLA-4), CAR-T cell therapy (patient's T lymphocytes modified to express a tumor-specific chimeric receptor), and cytokines. Unlike chemotherapy, immunotherapy can generate durable responses (years) because it activates immunological memory.

CAR-T cells expand exponentially after infusion when they encounter tumor cells that express the target antigen (CD19 in B lymphomas, BCMA in myeloma). The dynamics follow a Lotka-Volterra model: CAR-T (predator) expand depending on the abundance of the tumor (prey) and destroy tumor cells with saturated kinetics. Tumor control requires k_kill × T_CAR > r (tumor proliferation rate): if CAR-Ts do not reach a critical number, the tumor can escape.

Cytokine release syndrome (CRS) is the most severe toxicity of CAR-T therapy: massive activation of macrophages and CAR-T produces a storm of IL-6, IL-1, IFN- high fever, hypotension, hypoxia (grade 34: systemic inflammatory response syndrome). The model quantifies IL-6 production as a function of CAR-T activity × tumor mass. Tocilizumab (anti-IL-6 receptor) reduces k_deg/increases IL-6 clearance and controls CRS within 2448 h without compromising antitumor efficacy.

Checkpoint inhibitors (anti-PD-1: pembrolizumab, nivolumab) block the PD-1/PD-L1 inhibitory signal that tumors use to 'turn off' infiltrating cytotoxic T lymphocytes. The PD-1 signal follows a Langmuir isotherm: PD1_signal = [PD-L1]/(K_PD + [PD-L1]). Anti-PD-1 competes for the receptor, elevating K_PD and reducing PD1_signal release of T_ef from blockade expansion and antitumor activity. The response to checkpoints correlates with tumor mutational burden (TMB): tumors with high TMB have more recognizable neoantigens.

The abscopal effect (from Latin: 'off target') is the response of distant metastases when treating a single tumor with local radiotherapy: RT releases tumor antigens (immunogenic cell death) that activate tumor-specific CD8+ T lymphocytes, which systemically disseminate and attack the metastases. This effect is rare with RT alone but is dramatically amplified with the RT + anti-PD-1 combination. The pharmacokinetics of monoclonal antibodies (t½_ 24 weeks for therapeutic IgG1) allow dosing every 26 weeks.

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