How Immunotherapy Works Against Cancer — What Is Actually Happening in the Body

The immune system destroys abnormal cells constantly. Cancer is partly a story of how some cells learn to hide from this surveillance — and immunotherapy is the attempt to undo that hiding. But the mechanism is more specific than a general immune boost, and understanding exactly what happens makes the treatment more comprehensible.

Cancer's Evasion Strategy

Immune T cells patrol the body looking for cells that display abnormal proteins on their surface. Cancer cells, having accumulated mutations, often do display abnormal proteins. But they also develop ways to avoid being killed.

The most well-understood evasion: cancer cells express a protein called PD-L1. PD-L1 docks with a receptor called PD-1 on the surface of T cells. When this binding happens, it sends an inhibitory signal — the T cell essentially receives a message saying "stand down, I'm normal tissue, don't attack me." The T cell backs off. The cancer cell survives.

This is not a flaw in the immune system. PD-1 and PD-L1 exist to prevent the immune system from attacking healthy tissue. Cancer cells have hijacked a normal safety mechanism.

What Checkpoint Inhibitors Do

Checkpoint inhibitor drugs block this interaction. An anti-PD-1 drug (pembrolizumab, nivolumab) binds to the PD-1 receptor on the T cell, physically preventing PD-L1 from docking. An anti-PD-L1 drug (atezolizumab) binds to PD-L1 on the cancer cell, blocking it from reaching PD-1.

Either way: the inhibitory signal is cut off. The T cell is no longer being told to stand down. It recognises the cancer cell's abnormal proteins. It activates, proliferates, and kills the cancer cell.

The response can be dramatic because once the brake is released, the immune system does what it evolved to do — mount a sustained, specific attack. The T cells continue multiplying and attacking as long as they encounter the target. Some patients with Stage IV melanoma who were given months have been in durable remission for years on checkpoint inhibitors.

But this only works when there were T cells recognising the tumour in the first place. If the tumour has avoided immune recognition by a different mechanism — or if the tumour is simply not immunogenic — releasing the checkpoint does not help because there was nothing waiting behind it.

What Determines Whether a Patient Responds

1. PD-L1 expression: Tumours expressing high levels of PD-L1 are more likely to respond to anti-PD-1/PD-L1 drugs, but this is not absolute. PD-L1 testing is done by immunohistochemistry on the biopsy sample. High PD-L1 (≥50% expression) is required for pembrolizumab monotherapy in lung cancer without a targetable mutation.

2. Tumour mutational burden (TMB): The more mutations a tumour has, the more abnormal proteins it displays — and the more targets the immune system has to recognise. High TMB is associated with better checkpoint inhibitor responses across cancer types. Measured by next-generation sequencing.

3. Microsatellite instability (MSI-H): Tumours with defective DNA repair systems accumulate large numbers of mutations rapidly. MSI-H tumours — regardless of which organ they started in — respond to pembrolizumab. This is the basis for the first tumour-agnostic cancer drug approval: pembrolizumab can be given for any MSI-H solid tumour, regardless of site.

4. Cancer type: Melanoma and certain lung cancers have strong checkpoint inhibitor response rates. Most pancreatic cancers, many brain tumours, and most colorectal cancers without MSI-H have largely not responded.

CAR T-Cell Therapy — Engineering the Attack

Checkpoint inhibitors work by releasing existing immune responses. CAR T-cell therapy manufactures a new, targeted immune attack from scratch.

T cells are collected from the patient's blood. In a specialised laboratory, they are genetically modified to express chimeric antigen receptors (CARs) — artificial receptors that bind to a specific protein on the surface of cancer cells. The modified cells are multiplied into the hundreds of millions and infused back.

Once inside the patient, these engineered T cells hunt any cell expressing the target antigen. They bind, activate, and kill. Then they proliferate further — making more copies of themselves to continue the attack.

CAR T-cell therapy has produced complete remissions in patients with diffuse large B-cell lymphoma and acute lymphoblastic leukaemia who had failed every prior treatment. These are real remissions, sometimes durable.

The serious risks: cytokine release syndrome — a massive inflammatory response as the CAR T cells activate — can be life-threatening. Neurotoxicity is another complication. Managing these requires experienced teams in facilities with appropriate monitoring capabilities. It is not a treatment to administer casually.

The Reality of Response Rates

Immunotherapy works for some patients and not others — and the proportions vary significantly by cancer type and biomarker profile.

In non-small cell lung cancer with high PD-L1 expression, pembrolizumab monotherapy produces responses in about 45 percent of patients. In melanoma, combined nivolumab plus ipilimumab produces objective responses in about 58 percent of patients. These are better response rates than most prior treatments for these cancers, but they are not majority responses.

For patients whose tumours do not express PD-L1 and are not MSI-H, checkpoint inhibitor response rates are much lower. Immunotherapy is not a universal cancer treatment — it is a highly effective treatment for patients with the right tumour biology.

Side Effects — Immune-Related Adverse Events

Because these drugs release immune brakes broadly, they can cause inflammation in healthy tissue. The pattern of toxicity is fundamentally different from chemotherapy.

Colitis — diarrhoea from immune inflammation of the gut lining. Can be severe.

Pneumonitis — immune inflammation of the lung. Can cause breathlessness. Sometimes confused with infection or tumour progression.

Hepatitis — elevated liver enzymes from immune-mediated liver inflammation.

Endocrine toxicity — thyroid underactivity (hypothyroidism) is common and permanent in most cases, managed easily with thyroxine. Pituitary inflammation (hypophysitis) is rarer but causes hormonal deficiencies requiring steroid replacement. Adrenal insufficiency.

Skin toxicity — rash, vitiligo. Usually mild.

Severe immune-related adverse events require stopping the immunotherapy and treating with steroids. Most resolve, though some — particularly endocrine effects — are permanent.

Patients receiving immunotherapy need monitoring by oncology teams experienced in recognising and managing these toxicities, not just the cancer.

Immunotherapy in Prime Medical's Network

Apollo Proton Cancer Centre, Chennai — Dr. Rakesh Jalali (Medical Director, Neuro Oncology, 28+ years, 300+ peer-reviewed publications) and Dr. Sapna Nangia manage complex oncology cases including immunotherapy-eligible presentations. Molecular testing — PD-L1, TMB, MSI — available.

Max Super Speciality Hospital, Saket, Delhi (JCI, NABH, NABL) — Dr. Rohit Nayyar handles solid tumour oncology including immunotherapy.

Fortis Memorial Research Institute, Gurugram (JCI, NABH, NABL) — Multidisciplinary tumour board review of immunotherapy candidacy.

Yashoda Hospitals, Hyderabad (JCI, NABH, NABL) — Dr. M. Suneetha coordinates cancer care including immunotherapy.

Sarvodaya Hospital, Faridabad — Dr. Vishnu Hari handles cancer care for patients prioritising accessible pricing.

Fortis Hospital BG Road, Bengaluru — Dr. Niti Raizada and Dr. Saratchandra Pingali manage oncology including immunotherapy for Bengaluru-routed patients.

For patients from Ethiopia, Uganda, Tanzania, and Gambia who have received a cancer diagnosis and want to understand whether immunotherapy is relevant to their case: share biopsy and molecular testing results with Prime Medical Solutions. A specialist reviews within 48 hours.

To book a consultation, call the number on our website.