Immunotherapy is one of the most significant advances in cancer medicine in the last decade. It uses the body's own immune system to identify and destroy cancer cells — offering durable responses in cancers that were previously very difficult to treat.
Immunotherapy is a form of cancer treatment that activates, enhances, or restores the immune system's ability to recognise and destroy cancer cells. Unlike chemotherapy, which kills cancer cells directly, immunotherapy works by removing the brakes that cancer places on the immune system — allowing the body's own T-cells and immune cells to do the work.
Cancer cells are clever — they develop mechanisms to hide from or suppress the immune system. They display proteins called checkpoints (PD-L1, CTLA-4) that signal immune cells to stand down. Checkpoint inhibitor drugs block these signals, effectively "unmasking" cancer cells so the immune system can attack them.
The results can be remarkable — some patients with advanced cancers previously considered untreatable have achieved long-term durable remissions with immunotherapy. It is now a cornerstone of treatment in melanoma, lung cancer, bladder cancer, certain colorectal cancers, and many others.
Immunotherapy has transformed cancer care in ways that were unthinkable when I trained at Tata Memorial. The key for surgical oncologists is knowing when it can convert an inoperable tumour into an operable one — and timing surgery at the point of maximum response.
I also ensure that adequate tissue biopsy is obtained before treatment starts, so biomarker testing — PD-L1, MSI status, TMB — can guide whether a patient is likely to respond. The wrong treatment at the wrong time is as harmful as no treatment.
— Dr. Vinod T. Gore, MBBS MS FAIS FIAGES FARIS (Edin)Cancer evades the immune system through checkpoint proteins. Immunotherapy blocks these escape routes — restoring the immune attack.
Cancer cells display PD-L1 and other checkpoint proteins — signalling immune T-cells to ignore them, as if they are normal cells.
Checkpoint inhibitor drugs (e.g. Pembrolizumab) bind to PD-1 or PD-L1 — blocking the "don't attack me" signal cancer sends to T-cells.
With the brake released, T-cells recognise the cancer as foreign and mount a targeted immune attack against the tumour cells.
The immune system develops memory — continuing to fight cancer long after treatment ends, offering durable, lasting remissions.
Immunotherapy may be the primary treatment, used before or after surgery, or combined with chemotherapy — always guided by tumour biomarker testing.
Used as the primary treatment — either alone or with chemotherapy — in cancers with high PD-L1 expression or MSI-H status, often producing better results than chemotherapy alone.
Non-small cell lung cancer (high PD-L1), melanoma, MSI-H colorectal cancer, bladder cancer, renal cell carcinoma.
Primary TreatmentGiven before surgery to shrink the tumour and prime the immune system. Can convert previously unresectable tumours into operable ones — a major surgical opportunity.
Melanoma, non-small cell lung cancer, oesophageal cancer, triple-negative breast cancer.
Pre-operativeGiven after surgery to eliminate residual microscopic cancer and prevent recurrence — particularly effective in high-risk settings where recurrence risk is significant.
Resected melanoma, lung cancer, oesophageal cancer, bladder cancer post-cystectomy.
Post-operativeImmunotherapy and chemotherapy together are more effective than either alone in many cancers — chemotherapy may enhance tumour antigen release, boosting the immune response.
Lung cancer, gastric cancer, triple-negative breast cancer, cervical cancer, biliary tract cancer.
Combination TherapyImmunotherapy encompasses several distinct classes of drugs, each working through a different mechanism to engage the immune system against cancer.
| Type | How It Works | Examples | Used In |
|---|---|---|---|
| PD-1 / PD-L1 Inhibitors Most Common | Block the PD-1/PD-L1 checkpoint — preventing cancer from signalling T-cells to stand down. Unmasks cancer to the immune system. | Pembrolizumab (Keytruda), Nivolumab (Opdivo), Atezolizumab, Durvalumab | LungMelanomaBladderGastricColorectal MSI-H |
| CTLA-4 Inhibitors Checkpoint | Block CTLA-4 on T-cells — boosting early immune activation in lymph nodes and enhancing T-cell proliferation against the tumour. | Ipilimumab (Yervoy) | MelanomaLungRenal CellColorectal MSI-H |
| Monoclonal Antibodies Targeted | Engineered antibodies that bind specific cancer cell targets (HER2, VEGF, EGFR) — blocking growth signals or flagging cancer cells for immune destruction. | Trastuzumab (HER2), Bevacizumab (VEGF), Cetuximab (EGFR), Rituximab (CD20) | HER2+ BreastColorectalLungLymphoma |
| CAR-T Cell Therapy Cellular | Patient's own T-cells are extracted, genetically engineered to recognise cancer, multiplied in the lab, and infused back to attack specific cancer cell targets. | Tisagenlecleucel (Kymriah), Axicabtagene ciloleucel (Yescarta) | B-cell LymphomaALLMultiple Myeloma |
| Cancer Vaccines Therapeutic | Train the immune system to recognise specific tumour antigens — stimulating an immune response against cancer cells carrying those markers. | Sipuleucel-T (Provenge), Personalised neoantigen vaccines (investigational) | ProstateMelanomaClinical Trials |
| Cytokines Immune Signal | Signalling proteins (IL-2, Interferon) that stimulate immune cell growth and activity — amplifying the body's natural immune response to cancer. | Interleukin-2 (IL-2), Interferon-alpha, Pegylated Interferon | MelanomaRenal Cell CarcinomaHairy Cell Leukaemia |
Immunotherapy does not work equally in all patients or all cancers. Biomarker testing on tumour tissue helps predict who will benefit — making biopsy and tissue testing a critical first step.
High PD-L1 expression on tumour cells predicts better response to PD-1/PD-L1 checkpoint inhibitors. Tested by immunohistochemistry (IHC) on tumour biopsy.
IHC on biopsyMicrosatellite instability-high (MSI-H) and deficient mismatch repair (dMMR) tumours respond very well to checkpoint inhibitors regardless of cancer type — the first tumour-agnostic indication.
PCR or NGS panelTumours with a high number of mutations (high TMB) generate more neoantigens — making them more recognisable to the immune system and more responsive to immunotherapy.
Next-generation sequencingFor monoclonal antibody therapies, specific molecular targets must be present (HER2 overexpression, EGFR mutation). Testing ensures targeted antibodies have a specific target to bind.
FISH / IHC / NGSUnlike chemotherapy side effects (which affect rapidly dividing cells), immunotherapy side effects result from the immune system becoming overactivated — attacking normal organs alongside cancer. These are called immune-related adverse events (irAEs).
Early recognition is critical. irAEs can affect any organ — most commonly skin, bowel, liver, lungs, and endocrine glands. They can be mild or life-threatening. Patients must report any new symptom promptly. Most irAEs are fully reversible when caught early and treated with corticosteroids.
Inflammation of the bowel — diarrhoea, cramping, blood in stool. One of the most common irAEs. Managed with corticosteroids; severe cases may need infliximab.
CommonImmune inflammation of the lung — breathlessness, dry cough, reduced oxygen saturation. Can be severe. Requires prompt imaging and high-dose corticosteroids.
Watch CloselyElevated liver enzymes from immune-mediated liver inflammation. Usually asymptomatic and detected on routine blood tests. Managed with corticosteroids.
Moderate FrequencyThyroid dysfunction (most common — hypo or hyperthyroidism), adrenal insufficiency, or hypophysitis (pituitary inflammation). Often permanent — requires hormone replacement.
CommonRash, pruritus, and vitiligo (white skin patches — actually a sign of immune activity against melanoma). Usually mild. Topical steroids and antihistamines help.
Most Common irAEImmune inflammation of the heart muscle — rare but potentially life-threatening. Presents with chest pain, palpitations, or breathlessness. Requires immediate hospitalisation.
Rare — UrgentMost irAEs are manageable when identified early. Patients on immunotherapy should have regular blood tests, be given a clear list of symptoms to watch for, and have direct access to their oncology team. Immunotherapy is paused or stopped depending on severity, and corticosteroids are the mainstay of management.
A surgical oncologist's involvement in immunotherapy begins before the first dose is given — and extends to converting immunotherapy responders into surgical cure candidates.
If you or your family member has been advised immunotherapy, speak with Dr. Gore to understand how it integrates with your surgical treatment plan and whether biomarker testing has been done.