Tony Yang

7th Period
11/10/16
Independent Study: Track Hours
Source Number Letter: Source N
Citation: West H. Immune Checkpoint Inhibitors. JAMA Oncol. 2015;1(1):115.
Doi:10.1001. Jamaoncol. 2015. 0137
Source Validation: Source is published in a scientific journal and written by
multiple PhD scientists.
How did you find this source?: Through the use of Google Scholar
Intended audience: Other scientists studying in the field.
What arguments/topics does this source discuss?: The article first talks
about the immune system and its function inside of the body. It then discusses the
mechanisms that cancer cells use in order to evade the normal immune response of the
immune system. Then it goes on to talk about how checkpoint inhibitors can thus
function to allow for t-cells to not be inactivated. Finally, it goes on to talk about possible
immune system side effects that can occur from using checkpoint inhibitors.
Minimum 3 quotes, paraphrases, summaries of source text that seem likely
to be helpful in future writing:
"Conventional chemotherapy drugs often shrink a tumor within weeks, but immune
checkpoint inhibitors can take several months to work. These drugs can initially cause
the tumor to swell, making it appear that the tumor is growing. This is called
pseudoprogression. It occurs because of the large number of activated T cells and other
immune system cells and substances that enter the tumor. The brief increase in tumor
size may be followed by shrinking or eradication of the tumor."
T lymphocytes,or T cells, are immune system cells that can kill cancer cells. A T cell has
special locations on its surface called receptors. Other cells or molecules attach to these
receptors and turn the T cell on (activation) or off.
Some cancer cells bind to receptors on activated T cells and turn them off. Immune
checkpoint inhibitors are drugs that prevent cancer cells from turning off T cells. This
allows T cells to infiltrate a tumor and stop it from growing.
Reflection
This source was about 20 pages in fairly small font and was filled with acronyms and
many scientific terms that I was not familiar with. Also, there were many diagrams that
were present all throughout the article. For this reason, I spent about 4 hours altogether
reading and analyzing through the text.
`

Source Number Letter: Source O

 Citation: Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2015). Immune

checkpoint blockade: a common denominator approach to cancer therapy. Cancer
cell,27(4), 450-461.
Source Validation: Source is published in the scientific journal Nature and
written by multiple PhD scientists.
How did you find this source?: Through the use of Google Scholar
Intended audience: Other scientists studying in the field.
What arguments/topics does this source discuss?: The article begins by
giving a brief overview of the immune system and the inhibitor ligands that stop it from
functioning. While these inhibitors are present for a reason, cancer cells take advantage
in the sense that they can essentially deactivate the immune response to allow
themselves to continue growing uncontrollably. The article then discusses two
checkpoint inhibitors that have had great clinical success, anti-ctla-4 and anti pd-1. The
article then discusses the differences and similarities that exist between the two
checkpoint inhibitors
Minimum 3 quotes, paraphrases, summaries of source text that seem likely
to be helpful in future writing:
The PD-1 system of immune modulation bears similarities to CTLA-4 as well as key
distinctions. Similar to CTLA-4, PD-1 is absent on resting nave and memory T cells and
is expressed upon TCR engagement. However, in contrast to CTLA-4, PD-1 expression
on the surface of activated T cells requires transcriptional activation, and thus is delayed
(612 hr)
The immune system recognizes and is poised to eliminate cancer, but is held in check
by inhibitory receptors and ligands. These immune checkpoint pathways, which normally
maintain self-tolerance and limit collateral tissue damage during anti-microbial immune
responses, can be co-opted by cancer to evade immune destruction
The rapid-fire clinical successes from blocking CTLA-4 and PD-1, the first checkpoint
receptors to be discovered, have opened prospects for extending the potential of cancer
immunotherapy by inhibiting more recently discovered checkpoint ligands and receptors.
It is clear that despite some commonalities, CTLA-4 and PD-1 have distinct patterns of
expression, signaling pathways, and mechanisms of action. Although discovered over 20
years ago, there are still many unanswered questions about their biology, particularly in
the context of cancer.
Reflection
This source spanned the course of about 8 pages and talked about immune checkpoint
inhibitors. The promising results shed further light on how these drugs could eventually
lead to a prominent cure for cancer. It took me about two hours to completely finish
reading this article and analyze its contents.

Source Number Letter: Source P

 Citation: Brahmer, J. R., & Pardoll, D. M. (2013). Immune checkpoint inhibitors:

making immunotherapy a reality for the treatment of lung cancer. Cancer immunology
research, 1(2), 85-91.
Source Validation: Source is published in a scientific journal written by multiple
PhD scientists.
How did you find this source?: Through the use of Google Scholar
Intended audience: Other scientists studying in the field.
What arguments/topics does this source discuss?:
The article first quickly briefs over the past history of immunotherapy in treating cancer.
The article then talks about past problems with attempting to utilize immunotherapy in
the treatments of lung cancers and the obstacles that must be overcome. Next, the
article goes on to discuss the effectiveness of anti-CTLA-4 on lung cancer. Lastly, it
transitions into talking about the effectiveness of Anti-PD-1 and Anti-PD-L1 antibodies
before transitioning into talking about future prospects for the use of checkpoint inhibitors
in curing cancer.
Minimum 3 quotes, paraphrases, summaries of source text that seem likely
to be helpful in future writing:
Suppression of the antigen-presenting machinery is likely a particularly important
immune resistance mechanism for smoking- and pollution-associated lung cancers
because these tumors possess among the highest density of missense mutations in
expressed genes of any cancer type (roughly 12 mutations per megabase of expressed
exonic sequence;
Despite the limited success of immunotherapies in solid malignancy, two human
cancers, melanoma and renal cancer, have, for many years, responded to systemic
administration of immune-targeted biologics and showed signals of response to certain
therapeutic vaccines
Results from the past 3 years have not only validated the clinical potential for
immunotherapy but also the sense that we are just scratching the surface. Lung cancer,
the number one cancer killer in the United States and worldwide, has been the frontier
for immunotherapy's leap beyond the melanoma and renal cancer and will continue to
provide vistas for future innovation in this burgeoning field.
"
Reflection
This article was 10 pages and detailed an overview of the use of checkpoint inhibitors in
curing lung cancers. Like many other articles Ive read it is filled with academic
vocabulary and acronyms that I have never heard of. This slows down the reading
process and makes it so that I have to spend significantly more time to read. Overall it
took me about two hours to read through this article.

Reflection
In doing independent research, I was the only person that worked on my track work. For these
last eight track hours. I read through three scholarly articles published by doctorates in various
scientific fields. The articles that I read through took me about eight hours to go through
collectively and each varied in its length with the first article being considerably longer than the
other two. For these track hours, I put all my focus to an interesting biotechnology development
known as immune checkpoint inhibitors. This development was put to my attention through the
last meeting that I had with my mentor. In questioning him what the most promising
development in the treatment of cancer was, he responded that the answer to this question in
his opinion was checkpoint inhibitors. Essentially how checkpoint inhibitors function is through
the inhibition of specific antigens. While normally the body is able to fight off foreign cells, the
reason that the immune system is usually powerless to cancerous tumors is due to the tumors
property of being able to deactivate the t-cells, essentially rendering them useless against the
tumor. Where immune checkpoint inhibitors come in is through their ability to prevent the
deactivation of the t-cell from occurring. Thus, Checkpoint inhibitors are essentially drugs that
can bind onto either the t-cell receptor or the cancer cell antigen to prevent the deactivation of
the immune system. While this idea is relatively simple, the effectiveness in preliminary trials
has been outstanding and extremely promising for future use. Checkpoint inhibitors do not face
many of the problems that t-cell therapy faces due to the way it targets cancer cells. While the
use of immune checkpoint inhibitors will initially cause tumors to swell and enlarge themselves,
many trials have shown great effectiveness in using them. The primary targets for checkpoint
inhibitors is CTLA-4 and PD-1, this is why the checkpoint inhibitors that inhibit these two binding
sites are known as anti CTLA-4 and anti PD-1 respectively. There are many more binding sites
that have yet to have been discovered as mentioned by many of the articles, however with more
research and funding put into checkpoint inhibitors, they could one day serve as the primary
treatment to curing cancer in place of traditional methods like chemotherapy, radiation therapy,
or surgical removal of the tumor. Results from trials have not only been promising, but they
demonstrate many further implications for the use of immune checkpoint inhibitors for other
diseases. I accomplished these track hours in the comfort of my own house in front of my
computer. All of the research that I did for these eight track hours came over the course of a two
week period as I slowly read articles and carefully and thoroughly analyzed them. I chose to do
independent research as I felt that it was the only feasible option to accomplish my track work
for capstone. Not only that theres no way for me to do product creation in a topic like this. On
the other hand, internships were not available to me despite the fact that I emailed many
professors.