Immunotherapy and Emerging Treatments

Cancer immunotherapy harnesses or augments the immune system to recognise and destroy tumour cells. The field has been transformed by immune checkpoint inhibitors (ICIs), which release inhibitory brakes on T-cell activity.

The PD-1/PD-L1 axis is the dominant checkpoint targeted clinically. PD-1 (programmed death-1) is an inhibitory receptor expressed on activated T cells. Its ligand PD-L1 is expressed on many tumour cells — a mechanism tumours exploit to evade immune surveillance. Anti-PD-1 antibodies (pembrolizumab, nivolumab) block this interaction, restoring T-cell cytotoxic activity. Anti-PD-L1 antibodies (atezolizumab, durvalumab) achieve the same endpoint by blocking PD-L1 on tumour cells. In New Zealand, pembrolizumab is Pharmac-funded for several indications including non-small cell lung cancer (NSCLC) with PD-L1 ≥50% (first line), advanced melanoma, and MSI-H/dMMR tumours across tumour types (tumour-agnostic approval). Nivolumab is funded for relapsed/refractory classical Hodgkin lymphoma and advanced renal cell carcinoma.

CTLA-4 (cytotoxic T-lymphocyte antigen-4) is an earlier immune checkpoint that competes with CD28 for B7 ligands on antigen-presenting cells, downregulating T-cell activation. Ipilimumab (anti-CTLA-4) was the first ICI approved (2011, melanoma). Combination ipilimumab + nivolumab is funded in NZ for advanced melanoma and RCC.

CAR-T cell (chimeric antigen receptor T cell) therapy is a personalised cellular immunotherapy. Patient T cells are harvested, genetically engineered ex vivo to express a synthetic receptor targeting a tumour antigen (most commonly CD19 in B-cell malignancies), expanded in culture, then reinfused. CAR-T has produced remarkable responses in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukaemia (ALL). Currently not funded in NZ (as of 2026).

Cancer vaccines aim to induce antigen-specific immune responses. The most successful example to date is the HPV vaccine (Gardasil-9) — prophylactic, preventing cervical cancer by targeting HPV 16 and 18. Therapeutic cancer vaccines (e.g., sipuleucel-T for prostate cancer) remain of limited efficacy.

Immune-related adverse events (irAEs) result from loss of self-tolerance and affect any organ. Common: immune-mediated colitis (diarrhoea), pneumonitis, endocrinopathies (hypothyroidism, type 1 diabetes, adrenal insufficiency, hypophysitis), dermatitis, hepatitis. Management: grade-based — mild irAEs: hold ICI, supportive care; moderate: hold ICI, commence prednisolone 0.5–1 mg/kg; severe/life-threatening: high-dose methylprednisolone IV, consider infliximab for colitis, specialist input.

Biomarkers predicting ICI response: PD-L1 expression (tumour proportion score or combined positive score); tumour mutational burden (TMB-H: ≥10 mutations/megabase) — high TMB tumours generate more neoantigens; microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR) — highly responsive to pembrolizumab regardless of tumour type.