I was asking myself a very basic question, whether or not the pH level of the micro-environment would not be responsible for the inhibition of the killer cells against tumors. After several readings, including some documents and theses (theories) of Warburg, Vincent and Reding and the upholders of alkalinization. I realized that both parts spoke about the same topic, but on different grounds! Some people speak about the blood pH level (7.2 to 7.4 in both situations if the level goes behind these limits the individual will go into a coma situation) and the others speak about the extra-cellular pH (6.7, 6.8) A normal cell pH is 6.4) ; and interestingly the plant soil pH level is 6.3.
My two hypotheses were at first that I suspected this!
A too acid extra-cellular environment (less than 6.8) prevented "T cells NK" from penetrating into this micro-environment without dying from it; this too acidic micro-environment prevented them from reaching the tumor cells!
I juggled with the hypothesis that the pH level of the micro-environment might be the trigger for some normal cells to become cancer cells in order to survive in a hostile micro-environment?
After many readings (scientific literature), I fell on this search (research) in particular, which does not confirm my hypotheses, but which explains the processes and the mechanisms in action.
" Killer cell generation depends on extra-cellular pH. LAK precursor cells exist in peripheral blood, in almost all lymphoid organs and also in the tumor micro-environment. However, as the local pH within solid tumors is often acidic, we were interested in the influence of declining pH on generation of LAK cells. For this purpose, PBMC were cultured without and with IL-2 for 3 days at pHe ranging from 7·2 to 6·5. In a preliminary study we could show that the interaction between IL-2 and IL-2 receptor is completely inhibited at pH below 6·5. Respective data are soon to be published separately."
I don't have the answer because I don't have any lab, but I base my hypothesis on the fact that the blood stream travel in one way, I do suppose that microenvironment fluid follows the same rule?
This question is interesting as much as it is complicate to answer.
First of all, not ALL tumors create acidic extracellular environments.
This kind of environments is produced especially in the early stages of the tumors, when the tissue can b classified as hypoxic.
And another requirements is a strong aerobic glycolysis, which produces high amounts of lactate.
If your question is which kind of pH can be expected in such an extracellular environments, there is a good review from Moreno-Sanchez et al (FEBS Journal 274 (2007) 1393–1418).
Hi Fabrizio,
Thank you for taking your time to answer my question
Best Jean
Tumor immune evasion mechanisms are well documented. The quoted reference is not exactly relevant as it just describes a process for growing Lymphokine Activated Killer cells at various pHs. NK immunity is relevant in cancer because many cancer cells down regulate MHC II and NK cells are programmed to kill tumour cells lacking MHC II. IL-2 is but one path for activation of immune cells but this one pathway seems to be affected by pH as you say. However, there are alternative pathways such as engagement of the CD3 receptor along with a co-stimulant such as CD28 amongst many others that allow for activation outside of the IL-2 pathway.
In regards to your hypothesis, if you look at biopsies taken from tumours, you actually always find the tumour cells completely infiltrated with immune cells. I think this fact sufficiently falsifies your hypothesis. That the microenvironment of the tumour has lowered pH is a fact but this doesn't prevent infiltration by immune cells.
The transformation of normal cells into cancer cells is highly complex and I am not sure about the affect of pH on this process. It would be surprising to me if this was an issue because various tissues in the body routinely experience low pH, i.e. muscle cells from lactic acid production, etc. so I think that question is unresolved at best.
Thank you Daniel for the answer.
As for my hypothesis since I never had the chance to see any biopsy I didn't know the fact that odour were packed with immune cells. By the way, are those immune cells dead?
No they are alive. We believe they do not kill the tumour because the cancer cells are secreting IL-10 homologs that steer the immune response away from TH1 (cellular) immunity towards TH2 (humoral) response which is the exact same way the placenta steers the mothers immune response away from the "foreign" fetal tissue which contains 50% foreign DNA from the mother's immune cells' perspective.
Does the fact of changing the pH level has an impact on the effectiveness of a treatment for example Carboplatin or any other compound on the market for treating cancers?
Здравствуйте!
Я Вас нашел! Диалог и последовательность, мне очень приятна, с Вами!!! На Ваш вопрос в актуальности кислот ДНК-РНК и так далее, имею в виду кислот или рН...Это имеет существенное значение для любого организма!
С Уважением,Алексей.
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