Signs That Immunotherapy Is Working: What to Look For and When
Starting cancer treatment of any kind is an act of courage. But once treatment begins, anxiety shifts from “will I do this?” to “is this doing anything?” Waiting for results — watching your body for signs, dreading the next scan — is one of the most psychologically demanding aspects of cancer treatment.
Immunotherapy, in particular, can be confusing to interpret. Unlike chemotherapy, which begins affecting tumour cells almost immediately, immunotherapy builds a biological response over weeks and months. Understanding what to look for — and just as importantly, what not to misinterpret — can significantly reduce anxiety and help you stay accurately informed about your progress.
At Denvax, we have monitored hundreds of patients through immunotherapy treatment. This article reflects what we observe clinically and what the evidence tells us about how to assess whether immunotherapy is working.
Why Immunotherapy Response Looks Different from Chemotherapy?
With chemotherapy, the mechanism is direct: the drug kills rapidly dividing cells. Tumour shrinkage (if it occurs) typically appears on imaging within the first few treatment cycles. The response is relatively fast.
With immunotherapy, the process is fundamentally different:
1. The treatment activates or educates immune cells
2. Those immune cells need time to proliferate and mobilise
3. They travel to the tumour site and begin attacking cancer cells
4. Inflammation occurs at the tumour site as immune cells engage
5. Over time, this process leads to tumour cell death and reduction in tumour bulk
This biological sequence takes time — often 3 to 6 months before tumour shrinkage is clearly visible on imaging. This creates an important challenge: in the early weeks of treatment, it can be difficult to tell whether the treatment is working.
There is also a well-documented phenomenon called pseudoprogression — where tumours appear to grow on early imaging, not because cancer is spreading, but because immune cells are flooding to the site and creating visible inflammation. Pseudoprogression is a positive sign — it means the immune system is engaging — but it is frequently misinterpreted as treatment failure by clinicians unfamiliar with immunotherapy response patterns.
This is one reason why immunotherapy should be monitored by specialists with specific experience in this field.
Positive Signs That Immunotherapy Is Working
1. Improved Energy and Quality of Life
One of the earliest and most meaningful indicators is how the patient feels. As the immune system begins effectively targeting cancer cells and the tumour burden starts to reduce, many patients report:
– Noticeably improved energy levels
– Reduced fatigue (distinct from any chemotherapy-related fatigue)
– Improved appetite and weight stabilisation or gain
– Reduction in pain, particularly bone pain or pain related to tumour pressure
These subjective changes often precede what is visible on imaging. If a patient reports feeling meaningfully better 6–10 weeks into treatment, that is worth noting carefully.
2. Reduction in Disease-Related Symptoms
Specific symptoms caused by the cancer — breathlessness from a lung tumour, abdominal discomfort from a liver lesion, difficulty swallowing from an oesophageal tumour — often begin to reduce before imaging confirms tumour shrinkage. These functional improvements are clinically significant.
3. Stable Blood Markers
Many cancers are associated with tumour markers that can be monitored in blood: CEA (colorectal), CA-125 (ovarian), PSA (prostate), AFP (liver), LDH (lymphoma, melanoma), and others. A declining or stabilised tumour marker trend over successive blood tests is a positive signal.
Note: tumour markers are not perfect — they can fluctuate for reasons unrelated to treatment response. They should be interpreted alongside other evidence, not in isolation.
4. Imaging Showing Reduced Tumour Size (After 3–6 Months)
The gold standard for assessing response remains imaging — CT scan, PET-CT, or MRI depending on the cancer type. For immunotherapy, the expected timeframe for visible response on imaging is generally 3–6 months, sometimes longer in patients who go on to have sustained remission.
The response criteria used for immunotherapy (iRECIST or irRC) are different from those used for chemotherapy (RECIST), specifically to account for pseudoprogression. A radiologist and oncologist experienced in immunotherapy response assessment should review these images.
5. Immune Activation Markers in Blood
Specialist monitoring can detect the immune activation that precedes tumour response. At Denvax, we monitor markers including lymphocyte subsets (CD4, CD8 T-cells), cytokine levels, and immune cell activity where clinically appropriate. Rising CD8+ T-cell counts, for example, suggest the immune system is being activated.
6. Fever and Mild Inflammatory Symptoms After Infusion
A mild fever, muscle aches, or brief flu-like symptoms in the 24–48 hours following a Dendritic Cell Therapy infusion are often a sign of immune activation — the body responding to the educated dendritic cells being returned to circulation. These symptoms are generally mild and self-limiting. Paradoxically, patients who experience these mild reactions may be more likely to mount a good immune response.
Signs That Require Prompt Evaluation
Immunotherapy can occasionally cause the immune system to become overactive — attacking healthy tissue as well as cancer. These immune-related adverse events (irAEs) are important to recognise and report promptly. They include:
Skin: Rash, itching, blistering (especially with checkpoint inhibitors)
Gastrointestinal: Persistent diarrhoea, blood in stool, severe abdominal pain
Respiratory: New or worsening breathlessness, dry cough (immune-related pneumonitis)
Liver: Jaundice, very dark urine, fatigue with abdominal pain (immune hepatitis)
Endocrine: Fatigue, headache, visual disturbance (thyroid, adrenal, or pituitary involvement)
Neurological: Unusual weakness, sensory changes, confusion
Most of these events are manageable when caught early. Do not dismiss them as unrelated to treatment. Contact your treatment team promptly if you notice any of these.
At Denvax, patients have direct access to our clinical team throughout their treatment — not just at scheduled appointments.
When Not to Panic: Common Non-Concerning Findings
Temporary worsening on early imaging: As explained above, pseudoprogression is a recognised and documented phenomenon. A tumour appearing larger on a scan at 6–8 weeks is not automatically evidence of treatment failure — particularly if the patient feels clinically better. Re-imaging at 12 weeks with response pattern assessment is standard practice.
Fluctuating tumour markers in the first 8 weeks: Markers can fluctuate early in treatment. A temporary rise followed by a decline is a recognised pattern. A single elevated marker in isolation should not prompt a change in treatment decision.
Fatigue in the first few weeks: Some fatigue is common early in immunotherapy as the immune system is being activated. This typically improves as treatment continues.
The Monitoring Schedule at Denvax
Our standard monitoring approach for patients receiving immunotherapy at Denvax:
Blood tests: Every 3–4 weeks for tumour markers, complete blood count, liver function, thyroid function, and immune markers.
Imaging: Baseline imaging before treatment begins, then at approximately 3 months and 6 months. Frequency adjusted based on cancer type and clinical response.
Clinical review: Regular appointments with Dr. Khan and Dr. Yaqin to assess symptoms, quality of life, and to review test results in context.
Patient-initiated contact: Our team is accessible between scheduled appointments. We encourage patients to contact us if they notice any new symptoms rather than waiting for their next appointment.
What Happens If Immunotherapy Is Not Working?
Honest communication is the foundation of our practice. If monitoring indicates that treatment is not producing the expected response, we have that conversation directly. Options at that point include:
– Adjusting the immunotherapy protocol (different antigen preparation, additional infusion cycles)
– Adding a complementary treatment (checkpoint inhibitor, targeted therapy)
– Reassessing biomarkers to understand why response has been limited
– Discussing alternative approaches
“Immunotherapy is not working” does not necessarily mean “nothing will work.” It means the current approach needs to be reassessed. Cancer treatment is an iterative process.
Frequently Asked Questions
Q: How quickly should I expect to see improvement from immunotherapy?
A: Most patients see measurable clinical improvement (energy, symptoms, markers) within 6–12 weeks. Confirmed tumour shrinkage on imaging typically appears at 3–6 months. Some patients have a slower initial response but go on to have durable, long-term benefit. The timeline varies by cancer type and individual biology.
Q: My tumour marker went up after starting immunotherapy — does this mean it is not working?
A: Not necessarily. Tumour markers can fluctuate in the early weeks of immunotherapy. An isolated rise in weeks 4–8 of treatment, in the absence of worsening clinical symptoms, is not automatically a sign of failure. It should be monitored across serial measurements and interpreted alongside imaging and clinical assessment.
Q: I feel better but the scan looks similar — is treatment working?
A: This is a common scenario and is generally positive. Clinical improvement often precedes imaging response in immunotherapy. The immune response building inside the tumour is not always immediately visible on standard CT imaging. Continue with the monitoring schedule and allow time for the imaging to catch up to the clinical picture.
Q: A tumour appeared to grow on a scan after 6 weeks — is this pseudoprogression?
A: Possibly. Pseudoprogression is well-documented in immunotherapy patients. It requires expert interpretation: comparing the pattern of change to immunotherapy-specific response criteria (iRECIST), assessing whether symptoms have worsened or improved, and making a clinical judgment about whether to continue. Do not make a treatment change decision based on a single early scan without specialist review.
Q: Is there a blood test that can tell me if immunotherapy is working before imaging?
A: Immune activation markers (lymphocyte subsets, circulating tumour DNA tests where available, specific cytokines) can provide early signals. Declining circulating tumour DNA (ctDNA) in particular is an emerging and promising early indicator of response. At Denvax, we incorporate blood-based monitoring alongside standard imaging.
Q: What if immunotherapy stops working after a period of good response?
A: Secondary resistance to immunotherapy — where an initial response is followed by eventual progression — is a clinical challenge. When this happens, we reassess the protocol, consider combination approaches, and evaluate whether newer treatment options are appropriate. Achieving an initial good response is itself significant — it demonstrates the cancer is immunotherapy-sensitive.
Monitoring Your Treatment at Denvax
If you are currently receiving immunotherapy and have questions about whether it is working, or if you are considering starting immunotherapy and want to understand the monitoring process in detail, we welcome you to speak with us.
Knowing what to look for — and having experts who can interpret what they find — makes a substantial difference to the treatment experience.
