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Blood histidine and immunotherapy in cancer: can it predict treatment response?
In short
Histidine is a natural substance in the body, an amino acid, meaning a “building block” used by the body to build proteins. It is also found in foods such as meat, fish, eggs, dairy, legumes, and whole grains.
In recent years, researchers have noticed that histidine levels in the blood may be related to how some patients respond to immunotherapy , especially treatments called immune checkpoint inhibitors .
This information is promising, but it does not mean that patients should take histidine supplements without a doctor’s recommendation .
What is checkpoint inhibitor immunotherapy?
Immunotherapy is a type of treatment used in some forms of cancer. Unlike chemotherapy, which directly attacks rapidly dividing cells, immunotherapy attempts to help the immune system recognize and destroy cancer cells.
Checkpoint inhibitors are drugs that “lift the brakes” on the immune system. Sometimes cancer uses certain mechanisms to hide from immune cells. These drugs help the body better see the tumor and fight it.
Examples of such treatments are drugs that act on PD-1, PD-L1, or CTLA-4.
What does histidine have to do with immunotherapy response?
Recent research suggests that patients who have higher levels of histidine in their blood may, in some cases, have a better response to immunotherapy.
Specifically, better histidine levels could be associated with:
- better activity of immune cells ;
- a more effective response against the tumor ;
- a longer period without worsening of the disease ;
- possibly, better survival in some patients treated with immunotherapy.
However, it is important to remember that histidine is only a possible indicator , not a guarantee. A patient with high histidine is not certain to respond to treatment, and a patient with low histidine should not assume that treatment will not work.
What does “plasma histidine level” mean?
Plasma is the liquid part of the blood. When doctors or researchers talk about plasma histidine , they are referring to the amount of histidine measured in the blood.
This analysis is not currently a routine test used in all clinics for immunotherapy selection. It is being studied as a possible biomarker .
A biomarker is a measurable sign in the body that can provide information about the disease or the chances that a treatment will work.
Why might histidine help the immune system?
The immune system needs energy and nutrients to function well. Immune cells, including those that attack tumors, need a suitable environment to be active.
Histidine could contribute to:
- supporting the functioning of T cells, i.e. some of the most important cells of the immune system;
- maintaining more effective immune activity;
- reducing immune cell fatigue during the fight against the tumor.
Simply put: a good level of histidine could help the “soldiers” of the immune system be better prepared to fight disease .
Histidine and histamine: they are not the same thing
It’s easy to get confused, but histidine and histamine are not the same thing.
- Histidine is an amino acid useful to the body.
- Histamine is a substance produced from histidine, involved in allergies, inflammation, and other body reactions.
In some situations, elevated histamine levels can have different effects than histidine. Therefore, it is not enough to simply say “more is better.” What matters is the balance in the body, the type of cancer, the treatment, the gut microbiome, and the overall condition of the patient.
The role of nutrition and the gut microbiome
Histidine is found in food, but its level in the blood does not only depend on what we eat. It can also be influenced by:
- digestion;
- liver and metabolism;
- inflammation;
- treatments;
- nutritional status;
- the bacteria in the gut, i.e. the microbiome.
The gut microbiome is made up of billions of bacteria that live in the gut. Some can influence the response to immunotherapy. That’s why researchers are increasingly studying the connection between diet, the microbiome, immunity, and cancer.
Should patients take histidine supplements?
Not without a doctor’s recommendation.
Even though histidine seems promising as an indicator of response to immunotherapy, it does not mean that histidine supplements are automatically beneficial for all patients.
Self-administration of supplements can be risky, especially in cancer, as the patient may have:
- other associated diseases;
- complex oncological treatments;
- liver or kidney problems;
- risk of drug interactions;
- metabolic imbalances.
It is safest to discuss any supplement, special diet, or major change in diet with your oncologist or a nutritionist specializing in oncology.
Can histidine replace tests already used in oncology?
No. At this time, histidine does not replace tests already used for treatment selection.
In oncology, doctors may use several markers, such as:
- PD-L1;
- MSI;
- TMB;
- specific genetic mutations;
- tumor type;
- stage of the disease;
- the patient’s general condition;
- blood tests;
- imaging results.
Histidine could become an additional marker in the future, an extra piece of the puzzle. But the treatment decision remains a complex one and must be made by the medical team.
What does this mean for the patient?
For the patient, the main message is the following:
The level of histidine in the blood could, in the future, help estimate the chances of response to immunotherapy, but it is not yet a standard test for all patients.
When should the doctor be notified during immunotherapy?
Immunotherapy can have side effects, sometimes related to the activation of the immune system. Tell your doctor if you experience:
- persistent diarrhea;
- abdominal pain;
- new cough or difficulty breathing;
- extreme fatigue;
- fever;
- skin rashes;
- yellowing of the skin or eyes;
- severe headaches;
- vision problems;
- significant dizziness;
- rapid weight loss.
Do not stop treatment or take medications on your own without talking to your medical team.
Conclusion
Blood histidine is a promising potential biomarker for response to cancer immunotherapy. Better histidine levels may be associated with more effective immune system activity and better outcomes in some patients.
Disclaimer
However, this information should be viewed with caution. Histidine is not yet a standard test, does not replace currently used oncological markers, and does not justify taking supplements without medical advice.
For patients, the most important step remains the discussion with the oncologist, who can correctly interpret the tests and recommend treatment according to each case.
Bibliography
- Metabolic determinants of cancer immunotherapy outcomes identified by plasma profiling , Nature Medicine .
- Immune checkpoint inhibitors: recent progress and potential biomarkers , PubMed .
- The blockade of immune checkpoints in cancer immunotherapy , Nature Reviews Cancer .
- Cancer Immunotherapy with Immune Checkpoint Inhibitors—Biomarkers of Response and Toxicity , Diagnostics .
- Development and Validation of Blood-Based Predictive Biomarkers for Response to PD-1/PD-L1 Checkpoint Inhibitors , PubMed .
Dr. Onisim Florin Senior Medical Oncologist