Immunosuppressive Cytokines

[pjoshea13]

New study below [1].

Immunosuppressive cytokines are associated with a poorer prognosis, but patients may benefit from immune modulation.

...

"Thirty-seven men with biochemically recurrent (BCR) prostate cancer who received 6 months of androgen deprivation therapy (ADT) and were monitored until the time to prostate-specific antigen progression (TTPP) were identified from a completed phase III trial (NCT00020085)."

"Median TTPP was 399 days (range, 114-1641). Median prostate-specific antigen (PSA) at baseline and progression were 8.5 and 5.3 ng/mL, respectively. Twenty-three patients (62%) achieved undetectable PSA with ADT. Castrate levels of testosterone (<50 ng/dL) after 3 months of ADT occurred in 35 patients (95%). TNF-α .., IL-23 .., and CXCL10 ... significantly increased from baseline to post ADT."

"Patients with a detectable PSA after ADT had elevated levels of IL-6 ... and IL-8 ... at PSA progression as compared with those with an undetectable PSA. There was a trend toward shorter TTPP in patients with TNF-α levels above the median"

...

In a similar study from 2006:

"A significant proportion of men undergoing ‘curative’ radical prostatectomy (RP) for organ-confined prostate cancer relapse within 5 years. A number of adverse risk factors have been identified, but to date no adjuvant treatment as improved the outlook for these men. We proposed that these patients, despite small tumour burdens, may be immunosuppressed from their cancer, which may be amenable to immune modulation."

"In comparison with controls, RP patients expressed higher levels of both T helper type 1 (Th1) (interleukin (IL)-2 and tumour necrosis factor-α) and Th2 cytokines (IL-4, -5 and -10) with little change after removal of tumour. Further analysis based on known poor-prognostic factors indicated a trend to expression of higher levels of Th2 cytokines IL-4 and IL-5 in worse prognosis patients rather than the mixed Th1/2 found across the whole cohort. Persistently high levels of both Th1 and Th2 cytokines were detected in RP compared to control patients, despite the removal of relatively small tumour burdens. Cytokine expression studies may be useful as surrogate marker of potential disease progression, and could be used to identify patients who may benefit from immune modulation post-surgery."

"Perturbed cytokine expression 6 weeks after surgery may be a useful surrogate marker to define those patients who may be at risk of progressive disease, and who could enter a randomized trial of an immune regulator or adjuvant hormonal or chemotherapy agents."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/318...

Prostate. 2020 Jan 3. doi: 10.1002/pros.23948. [Epub ahead of print]

Association between immunosuppressive cytokines and PSA progression in biochemically recurrent prostate cancer treated with intermittent hormonal therapy.

Hawley JE1, Pan S1, Figg WD2, Lopez-Bujanda ZA3,4, Strope JD2, Aggen DH1, Dallos MC1, Lim EA1, Stein MN1, Hu J1, Drake CG1,3,5.

Author information

1

Division of Hematology and Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York.

2

Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

3

Columbia Center for Translational Immunology, Columbia University Medical Center, New York, New York.

4

Graduate Program in Pathobiology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.

5

Department of Urology, Columbia University Medical Center, New York, New York.

Abstract

BACKGROUND:

Immunosuppressive cytokines have the potential to promote prostate cancer progression. Assessing their longitudinal changes may implicate mechanisms of progression, treatment resistance, and suggest new therapeutic targets.

METHODS:

Thirty-seven men with biochemically recurrent (BCR) prostate cancer who received 6 months of androgen deprivation therapy (ADT) and were monitored until the time to prostate-specific antigen progression (TTPP) were identified from a completed phase III trial (NCT00020085). Serum samples were archived at baseline, 3 months after ADT, and at TTPP. Cytokine concentrations were quantified using a 36-parameter electrochemiluminescence assay. The Wilcoxon signed-rank sum test was used to compare observations between time points. Kaplan-Meier analysis was used to calculate TTPP dichotomized by cytokine values above or below the median. Pearson's rank correlation coefficient was used to compare continuous variables.

RESULTS:

Median TTPP was 399 days (range, 114-1641). Median prostate-specific antigen (PSA) at baseline and progression were 8.5 and 5.3 ng/mL, respectively. Twenty-three patients (62%) achieved undetectable PSA with ADT. Castrate levels of testosterone (<50 ng/dL) after 3 months of ADT occurred in 35 patients (95%). TNF-α (P = .002), IL-23 (P = .002), and CXCL10 (P = .001) significantly increased from baseline to post ADT. Certain cytokines correlated longitudinally: TNF-α correlated with IL-23 (r = .72; P < .001) and IL-8 (r = .59; P < .001) from baseline to post ADT and to PSA progression. Neutrophil-to-lymphocyte ratio correlated with IL-27 (r = .57; P < .001) and MIP-3α (r = .56; P < .001). Patients with a detectable PSA after ADT had elevated levels of IL-6 (P = .049) and IL-8 (P = .013) at PSA progression as compared with those with an undetectable PSA. There was a trend toward shorter TTPP in patients with TNF-α levels above the median (P = .042).

CONCLUSIONS:

Several innate cytokines were associated with biochemically recurrent prostate cancer.

© 2019 Wiley Periodicals, Inc.

KEYWORDS:

IL-23; IL-8; TNF-α; biochemical recurrence

PMID: 31899823 DOI: 10.1002/pros.23948

...

[2] nature.com/articles/4500899

[Graham49]

Thanks Patrick

Do you have a view whether the higher levels of cytokines are causative of cancer progression or could they be symptomatic of the immune system fighting the cancer?

A quick internet search indicates that polyphenols inhibit cytokines. Then there's prednisone, which has already been shown to have anti cancer properties.

[pjoshea13]

Thanks IT!

For those who did not follow the link, here are the inhibitors (some of which I covered a few years back, in the context of PCa): -Patrick (perhaps Nalakrats will comment on Art's list)

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1. Hesperidin - Anti-IL-6 plus antiinflammatory and antioxidant effects.

2. EGCG

3. Pine Bark Extract/Grape seed Extract - IL-6 inhibitors that have overall similar effect and also on other inflammatory mediators.

4. Amla - is definitely an IL-6 inhibitor as well as a glutathione increaser and anti-inflammatory. I have written about the potential value of Amla in another post. Click on my blue B-1 capsule icon and search the drop down list of 10 current posts to find it.

5. Andrographis Paniculata - Anti-IL-6 effects as well as antiviral, antioxidant and antiinflammatory effects. 😋😋😋

6. Zinc - Inhibits IL-6 and has synergy with L-Lysine as an antiviral!!! One study has shown that zinc picolinate is a well absorbed form!😋😋😋

7. Vitamin D-3 - Anti-IL-6 and it won't hurt to be in the upper half of the reference range for the many potential health benefits for PWP that I have written about here: healthunlocked.com/parkinso... 😋😋😋

8. Fish Oil / Omega 3's

9. Boswellia Serrata

10. Curcumin

11. Magnesium

12. Licorice

13. Lithium

14. Luteolin

15. Fisetin

16. Trehalose

17. Vitamin E - It should be noted that vitamin C and E work together well!😋😋😋

18. Vitamin C - It should be noted that vitamin C and E work together well!😋😋😋

19. Quercetin - 3 to 7 grams per day as suggested by the video that is lower in this thread. Also helps to improve zinc absorption!😋😋😋

20. Melatonin - Inhibits IL-6 and other inflammatory mediators while possessing potent antioxidant effects.😋😋😋

21. Xylitol - Xylitol not only inhibits IL-6, but also has the potential to increase T-Regulatory T-Cells or Tregs which have the potential to limit or control inflammation.

22. Mannitol - Also used for relief of some PD symptoms!

23. L-Lysine - An amino acid that inhibits both IL-6 and IL-8. It also is antiviral, especially when combined with Zinc!😋😋😋

24. Eldebery Syrup which can be found in a popular form, Sambucol Elderberry. This one was supplied by forum member KERRINGTON!

25. Ginger Extract - An inhibitor of NF Kappa b, IL-6 and IL-8. This one was also contributed by forum member, KERRINGTON!

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