• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

Immune therapy lifts hopes in fight with cancer

natasa778

Senior Member
Messages
1,774
... The Buffalo, N.Y., gastroenterologist was told he had six months to a year to live and he took a leave from his job to reckon with the grim prognosis. Then his wife, a nurse, tapped her social network and learned about a doctor in Boston who was running clinical trials of experimental drugs that might help.
In June 2012, Eckert went to Massachusetts General Hospital for his first infusion of a drug designed to release a brake the cancer was using to suppress his body’s immune system, and evade attack. Now almost two years later, the cancer has vanished and Eckert, 70, is back skiing, flyfishing, and golfing.

“To me it borders on the miraculous, really, because I’ve had no side effects whatsoever,” he said.

Eckert’s treatment exemplifies a shift in the scientific strategy for fighting some cancers. Driven by fundamental research — much of it done in Boston — an immune therapy approach that was on the fringes of cancer therapy is suddenly the hottest trend in cancer drug development.

Last week, for example, Boston researchers presented data showing that nearly half of patients with advanced melanoma lived for two years after getting an experimental immune therapy called nivolumab, though multiple other therapies hadn’t worked for them. Last month, the Swiss drug company Novartis AG acquired immunotherapy company CoStim Pharmaceuticals in Cambridge for an undisclosed amount. And Agenus Inc. in Lexington recently announced it had acquired 4-Antibody AG, a European firm focused on developing immune-stimulating therapies.

The frenzy of activity is an abrupt change for a field that had made big promises but failed to deliver for years; researchers searching for ways to spark an immune system attack on cancer felt like they were in a small club of believers. ...

https://www.bostonglobe.com/metro/2...mune-system/vDttP3phfRt1J9pCzs0emM/story.html

“Suddenly there’s credibility to this whole field of cancer immunology,” Harvard’s Sharpe said. “That’s been a landscape change.”
 

natasa778

Senior Member
Messages
1,774
This explains why/how blocking PD-1 would help the exhausted immune system, at least in cases where chronic infection is behind the dysfunction:

in several chronic virus infections, like HIV or hepatitis C virus (HCV) infection in humans, virus-specific CD8+ T cells become functionally exhausted, which likely contributes to the inability of the host to eliminate the pathogen (1, 2). One mechanism leading to CD8+ T cell dysfunction is the ligation of inhibitory receptors that induce T cell exhaustion (35). Blocking such receptor–ligand interactions partially restores T cell function and reduces viral loads in chronically infected animals (3, 6). The inhibitory receptor that has been studied in most detail is programmed death-1 (PD-1), which is one of the prototypic inhibitory receptors described as a potent mediator of T cell exhaustion

http://www.jimmunol.org/content/187/7/3730.long
 

anciendaze

Senior Member
Messages
1,841
This is particularly interesting to me because of reports that CD8+ T cells are implicated in a number of diseases with suspected viral etiology. The grim truth is that the evidence mainly turns up at autopsy, when CD8+ T cells are found in places they do not belong, like dorsal root ganglia. A second aspect of this problem is that CD8+ T cells also invade endothelial tissues like the walls of blood vessels in some cases where viral etiology is suspected. There is a continuum between endothelial dysfunction and obscure heart problems like diastolic dysfunction, or even idiopathic cardiomyopathy. This makes them a common factor in some very difficult medical mysteries involving degenerative disease of either nervous systems (CNS or autonomic) or the cardiovascular system.
 

SOC

Senior Member
Messages
7,849
Interesting for us because CD8+ T cell "exhaustion" is the second common immune dysfunction in ME/CFS after low NK cell function/number. Whether the two different immune profiles indicated different illnesses, different stages of the same illness, or different bodily responses to the same illness is completely unknown, as far as I've seen so far.

As one of those with low CD8+ cell numbers, attributed by my doc to exhaustion from chronic infection, I'd love to have a crack at nivolumab. ;)
 

natasa778

Senior Member
Messages
1,774
Interesting for us because CD8+ T cell "exhaustion" is the second common immune dysfunction in ME/CFS after low NK cell function/number. Whether the two different immune profiles indicated different illnesses, different stages of the same illness, or different bodily responses to the same illness is completely unknown, as far as I've seen so far.

As one of those with low CD8+ cell numbers, attributed by my doc to exhaustion from chronic infection, I'd love to have a crack at nivolumab. ;)

It is currently in phase II or III for several types of cancer - this in addition to showing ""unprecedented response rates" in metastatic melanoma.

The maximum time the patients could get treatment was 2 years of continuous therapy and then everyone had to stop and be observed in the clinic. And without any further therapy, most of the patients remained in response for a very long time. In fact, one patient's tumor continued to shrink after the drug was stopped," she said.
These results suggest that nivolumab may turn out to be used as a kind of booster vaccine, where patients come back to get their immune system boosted.

"We don't know yet the best way to give drugs that block PD-1 or PDL-1, and it is possible that we should build in some kind of booster regimen, but we really don't know that yet. But in one melanoma patient, she did very well for a while but after she went off drug, about a year and a half later, she developed tumor progression, so we treated her with nivolumab and she re-responded.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
Interesting for us because CD8+ T cell "exhaustion" is the second common immune dysfunction in ME/CFS after low NK cell function/number. Whether the two different immune profiles indicated different illnesses, different stages of the same illness, or different bodily responses to the same illness is completely unknown, as far as I've seen so far.

As one of those with low CD8+ cell numbers, attributed by my doc to exhaustion from chronic infection, I'd love to have a crack at nivolumab. ;)
@SOC, were your CD8+ numbers high before they went low or were they always low?
 

SOC

Senior Member
Messages
7,849
@SOC, were your CD8+ numbers high before they went low or were they always low?
I've only had immune testing relatively recently -- post Valcyte. My CD8+ numbers have been low as long as they've been tested, so for a couple of years.
 

anciendaze

Senior Member
Messages
1,841
Taking two separate trends in scattered evidence together, I would guess that CD8+ T cell numbers in samples of peripheral blood were down because those cells were invading tissues rather than loafing around in the bloodstream. The cells were still in the body, they just weren't where they were expected to be, or where they were easy to measure.

This is a classic problem in biological measurements. You can build a theory based on the idea the cell numbers are deficient, or cells are inactive, simply because you are looking in the wrong physiological compartment. In fact they may be present in considerable numbers, just not where you looked, and quite active doing things you had not imagined. You can guess how much the resulting theories are worth.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
Taking two separate trends in scattered evidence together, I would guess that CD8+ T cell numbers in samples of peripheral blood were down because those cells were invading tissues rather than loafing around in the bloodstream. The cells were still in the body, they just weren't where they were expected to be, or where they were easy to measure.

This is a classic problem in biological measurements. You can build a theory based on the idea the cell numbers are deficient, or cells are inactive, simply because you are looking in the wrong physiological compartment. In fact they may be present in considerable numbers, just not where you looked, and quite active doing things you had not imagined. You can guess how much the resulting theories are worth.
Please print that on a T shirt and hand it out to med students on their first day of class before they learn to treat labs and not their actual live patients.
 

natasa778

Senior Member
Messages
1,774
more tidbits related to PD-1: blocking this receptors results in drastic lowering of viral loads in various types of infections (didn't come across any research on EBV or herpesviruses). It has been suggested as worth trialling for control of HIV and hepatitis

Here we report that serial dosing with anti–PD-1 antibodies for several weeks resulted in a significant drop in viremia in one of three treated animals. The virologic response was associated with recovery of intrahepatic CD4+ and CD8+ T-cell responses.


This paper
PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies
-
talks about PD-1 expression in various types of cancers, could again be relevant to ME considering different types mentioned here?

robust PD-L1 protein expression was found in the majority of nodular sclerosis and mixed cellularity CHL, primary mediastinal large B-cell lymphoma, T-cell/histiocyte-rich B-cell lymphoma, EBV-positive and -negative PTLD, and EBV-associated diffuse large B-cell lymphoma (DLBCL), plasmablastic lymphoma, extranodal NK/T-cell lymphoma, nasopharyngeal carcinoma, and HHV8-associated primary effusion lymphoma. Within these tumors, PD-L1 was highly expressed by malignant cells and tumor-infiltrating macrophages. In contrast, neither the malignant nor the nonmalignant cells comprising nodular lymphocyte-predominant Hodgkin lymphoma, DLBCL-not otherwise specified, Burkitt lymphoma, and HHV8-associated Kaposi sarcoma expressed detectable PD-L1.
 
Last edited: