Here's a link to a new report out of MD Anderson: B-cell enrichment predictive of immunotherapy response in melanoma, sarcoma and kidney cancer
Which states, in part:
Studies published today in Nature conclude that enrichment of B cells, a type of immune cell known for producing antibodies, in TLS was predictive of response to checkpoint blockade in patients with melanoma, soft-tissue sarcomas, and renal cell carcinomas.
Checkpoint inhibitors offer the potential for long-term survival to patients across many cancer types, but not all benefit equally. Researchers previously have identified several useful biomarkers of response, which are helpful in identifying patients that may or may not benefit from checkpoint blockade. The current studies conclude that the presence of B cells and their location within TLS, which act as a lymph node within the tumor, is critical for response to checkpoint blockade, suggesting a dynamic interaction between several components of the immune system.
Mature B cells in tumors of responders suggest active role in tumor immune response
An MD Anderson-led study found that B-cell markers were the most differentially expressed genes in responders relative to non-responders, and B cells in the tumors of responders appeared to be more mature and specialized. These findings were first presented at the 2019 American Association for Cancer Research Annual Meeting. “These findings open up a whole new area ― that B cells are actually big drivers in cancer immunotherapy, specifically checkpoint blockade,” said corresponding author Jennifer Wargo, M.D... “This could lead us to important biomarkers for therapy response as well as potentially new therapeutic options.”
The team analyzed samples from patients with advanced melanoma receiving neoadjuvant, or pre-surgical, checkpoint inhibitors as part of a clinical trial sponsored by MD Anderson’s Melanoma Moon Shot... The researchers also studied a group of patients with metastatic RCC being treated with neoadjuvant checkpoint blockade... Tumor samples were collected from patients at baseline and during treatment ...
In each cohort, the expression of B cell-related genes was significantly higher in responders and was predictive of response to checkpoint blockade. These findings were further corroborated in an analysis of curated melanoma samples from The Cancer Genome Atlas, in which high expression of B-cell markers was associated with significantly improved overall survival.
“These data indicate the importance of cell types other than T cells, such as B cells, in the anti-tumor immune responses generated by immune checkpoint therapies,” said Sharma. “There is a great need to identify biomarkers of response to therapy, and these data may allow for future studies focused on developing composite biomarkers that represent both the T- and B-cell responses.”
The researchers determined that B cells were localized in the TLS, and the density of B cells and TLS in the tumor was higher in responders. Further analysis of these infiltrating B cells showed that those in responders expressed more markers of mature and differentiated B cells, such as memory B cells and plasma cells.
“Through these studies, we find that B cells are not just innocent bystanders, but are themselves contributing in a meaningful way to the anti-tumor immune response,” said first author Beth Helmink, M.D., Ph.D., fellow in Surgical Oncology. [Red highlight = mine]
So - news, but not news. Meaning we've long known that there is a wide array of tumor markers and cells that determine response - whether these bits and bobs block the immune system and work to protect the tumor or facilitate immune response and try to do away with tumors in our body. It isn't surprising that B cells contribute to that as well.
Here are a zillion prior posts on such markers and cells, which begins with this from 2016: Biomarkers - blood components, circulating tumor cells AND of the tumor itself Biomarkers. Sounds important. What are they? What can they really tell us?
We know that everything from floating bits of DNA in our blood stream, to antigens, to eosinophils, to the absolute number of monocytes and lymphocytes, to neutrophils, to t cells, to myeloid derived suppressor cells can help or hurt us in the fight to rid ourselves of melanoma and other cancers. Speaking of MDSC - here's a bit of a definition: MDSC; the Most Important Cell You Have Never Heard Of However, if you are Jeff Weber or a reader of this blog - you have!!!
Here are a few reports on the mystery of the MDSC: Markers for response to immunotherapy: Increased eosinophils = good. Increased Myeloid Suppressor cells = not so good.
In fact, in looking at t-regs from the ratties in my study, from this report put out in 2014, My Nivo (Opdivo) trial - first dose - 4 years ago 12/29/2010 - thoughts... it was noted that:
MDSC (myeloid derived suppressor cells)
"There was a trend towards lower baseline MDSC levels in non-relapsing patients compared to relapsing patients." This bit of stuff and such along with other Treg/Tcell data comes your way thanks to us ratties sitting through leukapheresis twice during the trial. However, this is a bit I'm pretty psyched about. There is talk among melanoma big dogs that combining anti-PD1 with MDSC or T-reg depletion would make it more effective. I think that holds real promise. Though...once again...despite my blood and services having been rendered....I have no idea what my MDSC levels were. Still...I think this could be a real boon to future patients.
So, YES! Let's tweak our tumor battle field. Let's boost the cells that help us and diminish those that don't. I am confident that these tiny bits and bobs play a huge role in the lives of human ratties who respond to immunotherapy and those who don't. And, yes, MD Anderson, I've written about your Moon Shot, too - in 2012 ~ Melanoma. Moon Shot. Curiosity. Will.i.am. The best 5th grade teacher in the world.
C'mon Man!!! It's 2020!! While great strides have been made, we've got a long way to go! So let's get there! - c
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