B cells within the tumor aid response in patients with melanoma, sarcoma, and renal cell carcinoma

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

Sew Chaotically ~ This Winter's uniform! - Corduroy Lander Pants and soft Monroe Turtleneck

These Landers in a wide ribbed cord, with just a bit of stretch, first used in Roo's Jacket, have been FABULOUS in my winter wardrobe!!!  I've loved my Summer Landers, which I made full length.  These I made cropped and have already enjoyed them with boots, tennies, and brogues.  Given the thickness of the fabric, I made these with no pockets fore or aft.  I know some sewists can't bear to part with pockets, but I'm very happy with the choice for this pair.  Plus, if you're into the look of Anna Allen's much adored  Persephone Pants and already own the True Bias Lander Pant pattern, then this is a way to get that vibe without purchasing another pattern.  Just say'n!  I made my usual size 8, using the full 1 inch side seam that is given in the pattern to allow for easy modifications, taking an additional 1/4 inch to both side seams at the waist, grading to nothing where the top edge of the pocket would hit.  I used my own curved waist band.  I recommend interfacing both left and right pieces of the fly. (The pattern advises that you interface the left only.)

Now for the top!!!  The Tessuti Monroe Turtleneck; a FREE pattern y'all!!!   I made size 1, their xxs-xs-s, with no mods.  Many have noted the arms are quite slender and that is true!  I wanted you to be able to see how both garments fit on me - ergo the strange poses.  So yes, they are rather fitted.  Best to check some arm measurements before cutting your fabric.  The knit is a thin, gently slubbed soft cotton I think I picked up in Atlanta, but I'm honestly not sure!  Given its drapey quality I thought it would work well for the Monroe, but I didn't want a cowl neck!  To avoid that, I doubled the fabric there (so the neck is actually 4 layers of fabric) leaving the sleeves and bodice a single layer.

Given the thickness and slight stretch of this fabric, I chose to make the inner waistband from a nonstretch, thinner woven.  Plus, it's pretty!!!

Fun well fitting makes!  Sew chaotically!!! - les

Sew Chaotically! ~ 3/5's of Christmas sewing! M6044 and M7349

There was so much fun in this making!!!  I had it planned in my head for the longest!  FIRST!  There was fun FABRIC shopping in New York!!!!  We made a crazy trip in October that rambled from D.C. through Maryland, Delaware, New York, Connecticut,  Rhode Island, and back to New York that I have yet to share.  B was a trooper and plotted our fabric shopping course within the stores and without! Mood was uncharacteristically organized while B & J Fabrics was in a bit of a shambles.  Loved them both.  Just say'n!  We had a great time going through the excellent shirting at Mood. (The selection is amazing at B & J as well - it will just cost you more!) 

For the boys I used McCall's 6044 which I've made three times previously.  Once for the Jamester in a large exactly per the pattern and twice with some modifications to create a looser fit around the waist.  You can check those versions here:  Three MEN's shirts! Three happy boys! M6044  While the current makes are short sleeved, from prior experience the long sleeved style is drafted very well and goes together easily.  For those considering this make, you should know the pattern does not have a back yoke.  That makes it quick and easy to stitch, but if you feel you need the ease that a pleat below the yoke provides, you might keep that in mind.  For this round, I made J's in a large with no adjustments except for narrowing the collar piece starting at about 3 inches as you work toward the point since it seemed to flare out a bit too much.  I like that change and will keep it for all future makes.  For B, who has a tendency to dislike clothing to touch his body, I created a yoke from the existing pattern pieces and did indeed give him the more typical pleat found on a man's shirt.  While it turned out very well, I don't think it was necessary.  J's straight large fit him perfectly and that's probably what he'll be getting next time!

Aren't they the cutest???  (Didn't really intend for them to "match", but there you go!)

Very pleased with my pattern matching - gotta say!!!

When sewing for others I do tend to be more careful!  Didn't want to rip through those buttonholes!!!  Despite all my care, after making B's I realized I positioned his pocket on the "wrong" side.  Men's shirts with a single pocket typically place them on the left front!  Poor Bentie!  Oh well, live and learn!  He insists he doesn't mind!  HA!!!  I considered moving it, but feared puncture holes would remain in this fine and tightly woven shirting.

When purchasing Roo's fabric, I had B6680 in mind.  But, when I asked her preference, she wanted her TNT M7349!  The fit and flare shape IS perfect on on her and the pattern goes together perfectly!  Here's a link to prior makes:  Rose, a floral beauty!!! (Oh, and M7349.)  The only difficulty was quantity of fabric.  For some reason this lovely substantial perfect purple ponte with a nice drape from B & J was quite narrow and I had purchased only the 1.5 yards required for B6680 instead of the 2 3/8 needed for M7349!  YIKES!!  Definitely a "make it work" moment!!  I had to narrow the skirt a bit and make the "sleeve" with a smidge of navy ponte from my remnants.  Given the slight variegation in the purple and identical weight in the navy remnant - I think it works!!!  Leaving me just enough to make the neckband from the purple.

Aren't they a fab couple?

Her Daddy's girl!

Here's to many more fun makes and shared family time in 2020!  Live and sew chaotically! ~ les

High NLR associated with treatment failure in melanoma when treated with PD-1 as a single agent

We have known that an elevated neutrophil-to-lymphocyte ratio (NLR) is associated with decreased response to immunotherapy and shortened overall survival in melanoma patients for some time.  I first reported on it in this post from 2015 which also includes some basic information on neutrophils and lymphocytes generally:  Lab values that may predict response to Ipi/Yervoy????  Unfortunately, we have also learned that high baseline NLR has an adverse impact on melanoma peeps being treated with targeted therapy as well:  Neutrophil-to-lymphocyte ratio and outcomes in melanoma. Yep, AGAIN!!!!! (High baseline neutrophil-to-lymphocyte ratio predicts worse outcome in patients with metastatic BRAF-positive melanoma treated with BRAF and MEK inhibitors)

Since then, many posts have followed, including those out of ASCO 2019:   Posts addressing NLR and response in melanoma

Now, there's this:

High neutrophil-to-lymphocyte ratio (NLR) is associated with treatment failure and death in patients who have melanoma treated with PD-1 inhibitor monotherapy.  Bartlett, Flynn, Panageas, et al.  Cancer.  2019 Oct 4.  An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor survival in patients with cancer, including those who receive immunotherapies. The authors sought to investigate NLR as a biomarker of treatment outcomes in patients with melanoma who were treated with PD-1 inhibition. Patients undergoing initial treatment with PD-1 inhibitor monotherapy for stage IV melanoma at a single center from 2012 to 2015 were included. Clinical characteristics and the NLR at baseline and before subsequent treatment cycles were collected. The time to treatment failure (TTF) and overall survival (OS) were evaluated using Kaplan-Meier and landmark analyses. Among 224 study patients, 63 (28%) had a baseline NLR greater than/= to 5. The baseline NLR was significantly associated with Eastern Cooperative Oncology Group performance status and the number of involved metastatic sites. With a median follow-up of 39 months in survivors, a baseline NLR greater than/= to 5 was independently associated with shorter OS and TTF. An NLR increase greater than/= to 30% during the first 2 cycles of treatment was associated with worse OS (median, 47 vs 13.5 months) and a trend toward shorter TTF (12.8 vs 5.9 months). A combined baseline NLR greater than/= to 5 and an NLR increase greater than/= to 30% identified a small cohort with markedly shortened OS (median, 5.8 months) and TTF (median, 1.8 months). Elevated baseline NLR and an increased NLR early during treatment are prognostic for TTF and OS in patients who have melanoma treated with PD-1 inhibitor monotherapy. Combined, these biomarkers can widely risk-stratify patients for treatment failure and survival.

What is lacking in all this research is any precise answer as to what to do with this information.  If it were me, I would have docs follow my ratios, scary though that may be.  I don't think oncologists follow these labs consistently with an eye toward this result and I am certain that patients are not routinely made aware of such laboratory findings (much less their implications) when they are.  However, these lab values could be an important factor in decision making about whether or not to switch the type of therapy the patient in pursuing, look at clinical trial options, etc.  

Ain't nothing in melanoma easy.  For what it's worth ~ c

Sew Chaotically! ~ MAKING deets! The DRESS!!! MOB outfit and decor!

The making begins!!!  Rose and I looked through my patterns, mainly for me to get an idea about shapes she liked, but she ending up picking one!  I had every intention of taking her pattern shopping among the "bridal" selections - but she insisted she was set - so we were off!!!

It started with the veil that dear Kay contributed.  It was attached to a strange plastic and lace "crown" which was not what Roo envisioned at all, so I removed it and covered the edges in a satin ribbon.  Later...

...a bit of the ribbon used for her dress was hand stitched on.

Two combs like this one were hand stitched, side-by-side, to the inner aspect to keep it in place.

This old Butterick pattern was Roo's pick.  However, instead of the sash, she requested a corset look.  With some yellow cotton sateen that had a bit of stretch, from Fine Fabrics in Atlanta - we were off!!!

While not usually one for making a toile, this was not my usual sewing circumstance!!  And it was a good decision!!!  My first invisible zip ever!  Not bad, not perfect.  Though the zip was cream not yellow, cause that's what I had!  I made a larger size (12) than I thought we needed - on purpose - so I could learn where to tweak it.  And then there was the 'corset'!  The first trick was deciding where to place and space the loops.  Not too difficult.  Then, what to use.  I hit upon the idea of tiny elastic cord.  The sort you might use to loop over a button for a closure.  I hand stitched them to the seam and used tape to hold them in place for machine stitching the side seams.

Seems okay!

Here they are.  Pretty cute.  Hand stitched.  Then the seam was machine stitched and serged.

And here we are!  Hmm....  Poor Roo touched one of the loops and was horrified that she had ruined her dress when it popped out completely.  Apparently the processing of serging/trimming the seams had done away with my hand sewing in which I had carefully punctured the elastic and the round little buggers had just rolled away from the needle during machine stitching.  Further, the few that remained intact did not work at all!!!  Elastic is stretchy - DUH!!!  So NOT a good idea for a corset.  The dress was WAY too big - it is much pinned here in a fitting, but that was what I expected.  AND ~ I learned that I had misunderstood the length Roo wanted for THE dress!!!  She wanted above the knee and I had envisioned tea length.  Not to worry!  That's what a toile is all about, right?  In the end, I removed all the elastics and fitted this dress, with a length just below the knee for this version resulting in a very wearable cute yellow dress!!

The veil was perfect and this is where we decided to add the purple ribbon.

Back to the drawing board for those loops!!!  I had plenty of 3/8 inch, white satin ribbon.  SEW!  I folded it in half and carefully stitched it together.  Then stitched along the folded side at the same distance for a balanced appearance and strength.

I love Neena so much!!!!

The "toil" and benefits of a learning curve...

Voila! Better invisible zip installation!  And more hopeful about the result of the ribbon loops, hand basted in place in this pic.

YES!  Much better.  They look neat.  Stay in place.  (A rather simple but important requirement!!)  And ~ they work!!!  Fabric is a Rosie selected material from JoAnn's - categorized as a stretch denim by them but seems more like a stretch cotton sateen to me with it's sleek and semi-glossy finish.  It is completely opaque which is good as she wanted neither a lining nor a slip!  And while it is thick enough to have a nice structure, it drapes very nicely.

I ended up making a straight 10 and still had to take in the sides a bit to get the perfect fit.  Mannie is not quite the same size as Roo, but you get the idea!

I added a few sweet details.  And there was a use for a bit of that elastic!  HA!

Despite reading grey in this photo...a little 'something blue' was embroidered at the hem.

In the end...

...sew perfect!!!!

 
It was such a lovely experience to create this dress with and for my Rosie.  While it certainly isn't for everyone, I am really glad I did it.  I also made it several months ahead.  Which meant I didn't have a time crunch and knew we could go buy her something lovely if this process didn't work out! 

Next up, runners for her tables:

Using a variety of paints we had on hand (some for fabric and some not) B and I did as we were directed by the artist bride and had great fun painting away on jute burlap in smoke/charcoal that I cut in strips to fit the tables from Fabric.com.  We thought about finishing the edges with a hem or some such, but in the end left them raw.

They turned out pretty, didn't they?

With all that out of the way, I had time to consider what the MOB was to wear!  HA!  Jamie's peeps were partial to green and Roo's to purple with a background of grey for both. 

I considered wearing this dress, The Bristol Dress by Orageuse , but I had long been thinking of a pattern hack based on this inspo:














Orageuse even provides the deets in a tutorial! 

Armed with this perfectly purple sateen from JoAnn's, (no stretch in this one) I made this!  The fabric had a lovely sheen, though in truth it was a little too stiff for this application to be its best, but it worked!  I will definitely be making another one in a material with more drape.

I paired my new Bristol top with some much worn, but never blogged, Flint Pants from Megan Nielsen in a lovely grey crepe.  They started out full length and were worn that way for about a year until I decided they would be more versatile with a bit of a chop. Since then they have gone on dates with dressy heels and to the grocery with tennies! 

For fun, with just a smidge of fabric left over, I made ANOTHER Tate Top, from Workroom Social, to wear when we decorated the venue and got ready at home.  (I know, I have a strange addiction to Tates!)

There you have it!!!

Being a maker is fun!  The DRESS, the decor, the MOB outfit!  Oh!!  And, I did play a pretty substantial role in making the bride!  HA!!!  It was all so lovely!  Ever so blessed to get to share in the making of this special day!  May the coming year bring more fun adventures to all of us! 

Sew and LIVE chaotically!  Much love ~ les

Rose and Jamie's Wedding!!! Bridal fun ~ Moore Love!!!

Rosie's special day begins....

Bridal party besties are up and att'em ~

Something borrowed...

Years before Rosie was born, Granny gave me this ring, telling me the little box had held her own wedding ring and since that time contained the one you see here.  A ring that belonged to her mother, Lottie DeMeris Chandler, Rosie's namesake.  A mother my granny lost at the age of 5.  It didn't look the same then, with empty settings and the metal worn through.  Granny had hoped one day I would have it mended, and last year, B made it happen.  We added semi-precious stones in colors I think Granny would have liked and had the metal repaired.  It made the day even more precious when Rosie wore it as her special borrowed item.

The bride and her dear peeps ~

NONE of us would have made it through this day without the sweet powerhouse Joseph!!!  A man of MANY talents and the biggest heart!

This girl!!! Dania has been part of our world and Rosie's sister forever.  Her laughter and support are a joy to us all.  This day would have never been the same without her!

RUTHIE!!!  She and Rosie have a special bond.  So blessed that she could make the trip and share her heart with all of us!

Something old?  Sweet dainty opal earrings her daddy got her years ago.

Time for the dress!!!

Sister love!!! Gotta have my Ruthie by my side!!!

My two beautiful girls!

A little something blue!

I think she's ready!!!  As ever, when one is the photographer, we have no pics of dear Irina who shared our laughs and love during this special time and without whom we would not have these amazing photographs!  Thanks, Irina!!!

Now!  We gotta get this bride to the chapel!!!