Immunotherapy for Cancer: How It Works

Understanding checkpoint inhibitors, CAR-T cell therapy, and other immune-based treatments

Key Points

• Checkpoint inhibitors release the immune system's "brakes," allowing T cells to recognize and attack cancer cells.
• Immune-related adverse events (irAEs) can affect virtually any organ system — early recognition and steroid treatment are critical.
• MSI-H/dMMR is the strongest biomarker for checkpoint inhibitor benefit, applicable across all solid tumor types.
• CAR-T cell therapy has transformed outcomes in relapsed/refractory B-cell lymphomas, ALL, and multiple myeloma.
• Cytokine release syndrome (CRS) and neurotoxicity (ICANS) from CAR-T require specialized management at certified centers.
• Immunotherapy responses can be durable — some patients achieve long-term remission after a finite course of treatment.

The Immune System and Cancer

Under normal circumstances, the immune system continuously surveys the body for abnormal cells. Cytotoxic T lymphocytes recognize tumor-associated antigens presented on cancer cell surfaces and eliminate these cells. This process — immune surveillance — is a natural defense against cancer development. Cancers evolve mechanisms to evade this surveillance. One key mechanism is upregulation of programmed death-ligand 1 (PD-L1) on the tumor cell surface. PD-L1 binds to the PD-1 receptor on T cells, transmitting an inhibitory signal that effectively "turns off" the T cell — this is one of the…

Checkpoint Inhibitors

Multiple checkpoint inhibitors are now FDA-approved, spanning several distinct targets: PD-1 inhibitors: Pembrolizumab (Keytruda) and nivolumab (Opdivo) are the most broadly approved agents, with indications across melanoma, NSCLC, HNSCC, renal cell carcinoma, bladder cancer, gastric cancer, esophageal cancer, MSI-H solid tumors, TMB-H solid tumors, cervical cancer, TNBC, endometrial cancer, biliary tract cancer, and many others. Cemiplimab (Libtayo) is approved for cutaneous SCC, BCC, and NSCLC. PD-L1 inhibitors: Atezolizumab (Tecentriq), durvalumab (Imfinzi), and avelumab (Bavencio) block…

Immune-Related Adverse Events (irAEs)

The mechanism that makes checkpoint inhibitors effective — unleashing immune activity — is the same mechanism that makes them potentially dangerous. Without normal immune checkpoints, T cells can attack healthy tissues, producing a spectrum of "immune-related adverse events" (irAEs) that can affect virtually any organ system. Common irAEs include: dermatitis (maculopapular rash, pruritus — most common, often benign), diarrhea/colitis (ranging from mild loose stools to life-threatening colitis), hepatitis (transaminase elevation), endocrinopathies (hypothyroidism most common; hypophysitis,…

Biomarkers for Immunotherapy Response

Identifying which patients will benefit from checkpoint inhibitors is one of the most active areas of translational oncology research. Several biomarkers are in clinical use: PD-L1 expression (immunohistochemistry): Required for several indications (NSCLC, HNSCC, TNBC, cervical cancer) to determine eligibility or dosing strategy. However, PD-L1 is an imperfect biomarker — some PD-L1-negative tumors respond, and some PD-L1-positive tumors do not. Scoring systems (TPS, CPS, IC score) vary by drug and indication, creating complexity. MSI-H/dMMR (microsatellite instability-high / mismatch repair…

CAR-T Cell Therapy

Chimeric antigen receptor T-cell (CAR-T) therapy represents a fundamentally different approach to immunotherapy — engineering the patient's own T cells to recognize and attack specific tumor antigens. The process: blood is drawn from the patient through apheresis, T cells are isolated, genetically modified with a viral vector to express a synthetic receptor (the CAR) that directly recognizes a tumor surface antigen without MHC restriction, and then expanded to billions of cells over 2–4 weeks in a manufacturing facility. These engineered cells are then infused back into the patient after…

Other Immunotherapy Approaches

Beyond checkpoint inhibitors and CAR-T, several other immune-based therapies are in clinical use or active development: Bispecific antibodies simultaneously engage two targets, most commonly connecting CD3 on T cells with a tumor-associated antigen — physically bringing T cells into contact with cancer cells without requiring MHC-antigen presentation. Blinatumomab (Blincyto, anti-CD19/CD3) is FDA-approved for B-ALL. Newer bispecifics include glofitamab and epcoritamab (anti-CD20/CD3) for DLBCL, and teclistamab, talquetamab (anti-BCMA or GPRC5D / CD3) for multiple myeloma — representing a…