1. What data in particular will be shared?
   Response - All of the individual participant data collected during the trial, after de-identification.
   


2. What additional supporting information will be shared?
   Response -  Study Protocol
   Response -  Statistical Analysis Plan
   Response - Informed Consent Form
   Response - Clinical Study Report
   Response -  Analytic Code
   
   
3. Who will be able to view these files?
   Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.
   


4. For what types of analyses will this data be available?
   Response - To achieve aims in the approved proposal.
   


5. By what mechanism will data be made available?
   Response (Others) -  To avail data , the requestors could contact the principle investigator with a letter of request including a declaration on purpose and usage of date.


6. For how long will this data be available start date provided 09-01-2027 and end date provided 31-01-2031?
   Response - Beginning 3 months and ending 5 years following article publication.
   


7. Any URL or additional information regarding plan/policy for sharing IPD? 
   Additional Information - NIL

Chemotherapy, radiotherapy and surgery were the triad of cancer treatment in older ages. In 1890, the invention of Cooley, reporting the utilization of immune-stimulation in solid untreatable tumors, has revolutionized the cancer therapy. This particular treatment modality has been elaborated as immunotherapy. Ever since the introduction of immunotherapy, an intricate research has been carried out for decades which ultimately landed in targeting T cells. The conserved negative regulators of T cell activation are the primary targets of immunotherapy current date.

Cytotoxic T Lymphocyte Associated protein 4 (CTLA-4) was found to be an important co-stimulatory molecule of T cells, similar to Cluster of Differentiation 28 (CD28) (BOX1). CTLA-4 was proven to be inhibiting the activation and proliferation of T cells by multiple mechanisms i.e., by antagonizing the activity of CD28, by competitive inhibition of co-stimulatory ligands, prevention of immune conjugates and recruit inhibitory effectors. 

Combatively, CTLA-4 was considered an important “immune checkpoint molecule” and targeted for blockade in the treatment of cancer. James Allison and colleagues first invented that neutralizing anti-CTLA-4 antibodies had reported to elevate anti-tumoral immunity. In this core, a range of immunotherapy agents such as ipilimumab , tremulimumab, etc., are invented and invocated as a recommended primary care regimen for various cancers like melanoma, urothelial cancers, etc.,.

Despite the dynamics, various systemic inflammatory burdening conditions have been supposedly hypothesized to have a detrimental effect on immunotherapy outcomes. One such profound systemic inflammatory burden, affecting or having an impact on various systemic conditions is reportedly periodontitis. Periodontitis is a chronic immunoinflammatory condition incited by microbial origin. Dysbiosis is proven to be the key to trigger the inflammation cascade, leading to adverse profile of various inflammatory marker. To specific note on the area of research, Porphyromonas gingivalis, a keystone pathogen, has been proven in multitude to trigger an imbalance in systemic immunoinflammatory burden. The virulence factors of the microbe, specifically gingipains, Outer Membrane protein are said to trigger a wide array of molecular agent and one such key molecule is CTLA-4. Various literature evidence supports the elevation of CTLA-4 in the progression of periodontitis.

The systems biology model of periodontitis dictate the impact of systemic inflammatory profile on local condition and vice versa. By narrowing down the window of research, this local elevation of CTLA-4 in response to periodontitis, can supposedly elevate the systemic CTLA-4 profile. In patients undergoing cancer immunotherapy, this elevation could lead to compromised therapeutic outcomes of the immunotherapy drug.

However, this particular hypothesis despite being proposed theoretically, and reported as reviews, is not proven clinically. This throws an area of quench for evidences, despite the current period is an era of immunotherapy. Thus the current study is a first of its kind, to evaluate the confounding effect of periodontitis related elevation of CTLA-4 levels in the therapeutic outcomes in patients undergoing immunotherapy.

Aim: To evaluate the cofounding effect of elevated CTLA-4 in response to periodontitis on the altered therapeutic outcomes of cancer immunotherapy targeting CTLA-4

Null hypothesis: The levels of CTLA-4 reduction will not differ in cancer patients with and without periodontitis, being treated with anti-CTLA-4 immunotherpy. 

Alternate hypothesis : The levels of CTLA-4 reduction will be better in cancer patient who are periodontally healthy and undergoing anti CTLA-4 immunotherapy, when compared to those with periodontitis.