Insight: Training immune system to fight cancer comes of age | Reuters

 Blogger's Note: not specific to ovarian cancer

Insight: Training immune system to fight cancer comes of age | Reuters


".....While extending life is the gold standard, most cancer drug trials have been deemed successful if tumors shrink or if a treatment can demonstrate a delay in tumor growth or in worsening of the disease, known as progression-free survival (PFS).
But Provenge and Yervoy have extended survival without necessarily impacting PFS or tumor shrinkage in many cases.
"Overall survival is the accurate indicator. Tumors may look bigger because they are filled with immune cells, so they appear worse," said Wolchok. "We've proposed a new set of response criteria to try to incorporate some of this biology.".......

abstract: Effects on the immune system and toxicity of carboplatin/paclitaxel combination chemotherapy in patients with stage III-IV ovarian and non small cell lung cancer and its role in survival and toxicity.

 
Effects on the immune system and toxicity of carboplatin/paclitaxel combination chemotherapy in patients with stage III-IV ovarian and non small cell lung cancer and its role in survival and toxicity.


Abstract
 
Purpose:
To examine the impact of paclitaxel and carboplatin combination chemotherapy on the parameters of the immune system in patients with non small cell lung cancer (NSCLC) and with ovarian cancer before, during and after chemotherapy, and the effect of this combination on the overall patient survival.

Methods:
24 patients with NSCLC and 20 with ovarian cancer (all in stage IIIb-IV) treated with 6 courses of paclitaxel and carboplatin combination chemotherapy were separated into two groups according to their survival group A: long survival (> 12 months for NSCLC; > 30 months for ovarian cancer) group B: short survival (<12 months for NSCLC; <30 months for ovarian cancer).

At the same time we studied some immunological parameters (CD3, CD4, CD8, CD56, CD34, IL-3, IFN-γ) in relation with the induced toxicity during chemotherapy. The results were analysed using the ANOVA method.

Results: 
We observed a statistically significant difference of CD4 and CD4/CD8 after chemotherapy between groups A and B (p<0.001 and p< 0.006 respectively), implying that the further increase of T-helper cells after chemotherapy had a positive impact on survival. In addition, statistically interesting was the difference in values of IFN-γ between patients of groups A and B before and after chemotherapy (p< 0.039 and p< 0.027, respectively). Patients with high IL-3 had little chance of toxicity.

Conclusion:
Our findings support that with carboplatin/ paclitaxel combination chemotherapy, important parameters of the immune system (IFN-γ, CD4, CD4/CD8) can be used as prognostic factors for survival, while others (IL-3) as indicators of toxicity.

Single antibody (CD47 ) shrinks variety of human tumors transplanted into mice, Stanford study shows | e! Science News

Single antibody shrinks variety of human tumors transplanted into mice, Stanford study shows | e! Science News

Human tumors transplanted into laboratory mice disappeared or shrank when scientists treated the animals with a single antibody, according to a new study from the Stanford University School of Medicine. The antibody works by masking a protein flag on cancer cells that protects them from macrophages and other cells in the immune system. The scientists achieved the findings with human breast, ovarian, colon, bladder, brain, liver and prostate cancer samples. It is the first antibody treatment shown to be broadly effective against a variety of human solid tumors, and the dramatic response -- including some overt cures in the laboratory animals -- has the investigators eager to begin phase-1 and -2 human clinical trials within the next two years.........

open access: JTM - Absolute lymphocyte count is associated with survival in ovarian (SEROUS) cancer independent of tumor-infiltrating lymphocytes

  lymphocytesplural of lym·pho·cyte

Noun:

A form of small leukocyte (white blood cell) with a single round nucleus, occurring esp. in the lymphatic system.

 Abstract (provisional)

Background

The immune system strongly influences outcome in patients with ovarian cancer. In particular, the absolute lymphocyte count in peripheral blood (ALC) and the presence of tumor-infiltrating lymphocytes (TIL) have each been associated with favourable prognosis. However, the mechanistic relationships between ALC, TIL and prognosis are poorly understood. We hypothesized that high ALC values might be associated with stronger tumor immunity as manifested by increased TIL, decreased tumor burden and longer survival.

Conclusions

Patients with high intrinsic ALC values show no clinical or survival advantage upon subsequent development of HGSC. ALC values at diagnosis are prognostic due to an association with disease burden rather than TIL. Therapeutic enhancement of ALC may be necessary but not sufficient to improve survival in HGSC. 

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Traitorous Immune Cells Promote Sudden Ovarian Cancer Progression | Wistar

Wiki:  
Dendritic cells (DCs) are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells. They act as messengers between the innate and adaptive immunity.

  ~~~~~~~~~~~~

"Aggressive ovarian tumors begin as malignant cells kept in check by the immune system until, suddenly and unpredictably, they explode into metastatic cancer. New findings from José R. Conejo-Garcia's lab demonstrate that ovarian tumors don’t necessarily break “free” of the immune system, rather dendritic cells of the immune system seem to actively support the tumor’s escape. The researchers show that it might be possible to restore the immune system by targeting a patient’s own dendritic cells....."

abstract: Distinct Subpopulations of Epithelial Ovarian Cancer Cells Can Differentially Induce Macrophages and T Regulatory Cells Toward a Pro-Tumor Phenotyp

Problem  Presence of immune infiltrates in the tumor does not always correlate with an anti-tumoral immune response. (eg. vaccine therapies...)
Conclusion  We demonstrate that each ovarian cancer cell subpopulation can induce a unique phenotype of macrophages and T cells, both associated with tumor-supportive function.

Vaccines to boost immunity where it counts, not just near shot site | e! Science News

"It should not be long because all the individual cytokines (immune system factors) and additional materials loaded into these particles are already FDA approved for use in humans," Abraham said. "There is a lot of interest in nanoparticle-based therapy, but we are basing our materials on our observation of mast cells in nature. This is an informed application to deliver the right material to the right place in the body to get the most effective immune reaction."

Quantitative and Functional Alterations of Plasmacytoid Dendritic Cells Contribute to Immune Tolerance in Ovarian Cancer

Note: in research/technical

Abstract

"In ovarian cancer, the immune system fails to eradicate established tumors partly due to the induction of immune tolerance within tumor microenvironment.....cont'd

abstract: Intraoperative Neuraxial Anesthesia But Not Postoperative Neuraxial Analgesia Is Associated With Increased Relapse-Free Survival in Ovarian Cancer Patients After Primary Cytoreductive Surgery

Abstract

Objectives:  

Regional anesthesia has been shown to blunt the response to surgical stress and decrease the use of volatile anesthetics and the consumption of opioids, which may reduce immune compromise and potentially delay tumor recurrence. The goal of this study was to find a possible association between intraoperative regional anesthesia and decreased cancer recurrence.

Conclusions: 

Intraoperative use of epidural anesthesia was associated with an increased time to tumor recurrence after surgery in ovarian cancer patients. This may be a result of preservation of the immune system function.

The Wistar Institute has appointed ovarian cancer researcher José R. Conejo-Garcia, M.D., Ph.D., as associate professor in the Institute’s Immunology Program. | Medical Education

"....Conejo-Garcia’s laboratory program explores an innovative approach to fighting ovarian cancer by exploiting the tumor’s reliance on its “microenvironment,” the collection of neighboring, healthy cells that nourish the tumor and enable it to thrive. In particular, he has developed a “Trojan Horse” method that reprograms white blood cells within the microenvironment – which otherwise have the effect of preventing the spontaneous anti-tumor activity of the immune system – so that they activate immune cells to attack the ovarian tumor...."

CCR Connections (News at NIH) - A Cure for the Incurable? Using the Body's Immune System to Treat Metastatic Cancers