A technological breakthrough by medical researchers at Tel Aviv University enabled the discovery of a cancer mechanism that prevents the immune system from attacking tumors. The researchers were surprised to find that reversing this mechanism stimulates the immune system to fight the cancer cells, even in types of cancer considered resistant to prevailing forms of immunotherapy. The breakthrough was led by Prof. Carmit Levy, Prof. Yaron Carmi, and PhD student Avishai Maliah from TAU's Faculty of Medical and Health Sciences. The paper was published in the leading journal Nature Communications.

Prof. Levy: "It all happened by coincidence. My lab studies both cancer and the effects of ultraviolet (UV) radiation from the sun on our skin and body – both of which are known to suppress the immune system. Cancer suppresses approaching immune cells and solar radiation suppresses the skin's immune system. While in most cases, we cancer researchers worldwide focus on the tumor and look for mechanisms by which cancer inhibits the immune system, here we proposed a different approach: investigating how UV exposure suppresses the immune system and applying our findings to cancer. The discovery of a mechanism that inhibits the immune system opens new paths for innovative therapies".

What Surprising Findings Emerged from the Research?

Prof. Levy adds: "With this idea in mind, I asked my colleague Prof. Yaron Carmi, a global expert on the immune system, to join the study. Avishai Maliah, an MD/PhD candidate in my lab, led the project. The first stage was a comprehensive investigation of changes in the skin induced by exposure to UV, using a mouse model. Avishai examined the behavior of dozens of proteins post-UV exposure and surprisingly discovered a significant rise in the level of a relatively unexplored protein called Ly6a. This unexpected finding led us to investigate further, to understand the protein function and whether it is involved in the immune suppression process".

Prof. Carmi explains: "It's important to understand a basic aspect of the immune system's function. Our natural immune system is very efficient and very powerful, but it contains quite a few brakes and controls, to prevent overactivity that can cause autoimmune diseases – in which the body attacks itself. When our skin is exposed to UV radiation from the sun, our immune system responds immediately: blood vessels expand, DNA is repaired wherever possible, and cells with mutations are identified and removed. At the same time, a strong control system with numerous brakes is also activated to prevent overactivity".

How Does UV Exposure Affect Immune Response?

Prof. Levy: "The use of sunlight to suppress autoimmune diseases of the skin – when the skin's immune system overreacts - has been known for years. Phototherapy is basically the application of UV radiation to treat patients with autoimmune diseases, such as psoriasis, vitiligo and more, because ultimately UV suppresses the skin's immune system".

Avishai Maliah: "We found that after exposure to UV radiation, the immune system's T cells - that play a critical role in fighting cancer - begin to express high levels of the protein Ly6a. We suspected that Ly6a serves as a brake through which UV inhibits the immune system, and that by releasing this brake, optimal activation of the immune system might be resumed".

Prof. Levy: "We were surprised to discover that this protein, Ly6a, is also overexpressed in cancer tumors – apparently inhibiting T cells. Having found this in two types of cancer, melanoma skin cancer and colon cancer, we have reason to believe that the same thing happens in other cancers as well. Evidently, we have discovered a general mechanism through which cancer tumors desensitize the immune system. Avishai treated cancer with Ly6a antibodies, and amazingly the tumors were significantly reduced. Moreover, cancers resistant to known treatments reacted substantially to Ly6a antibodies". The new discovery can have practical implications in immunotherapy – treating cancer by enhancing the response of the immune system.

Prof. Carmi: "Immunotherapy has revolutionized the treatment of cancer. However, about 50% of the patients do not respond to the currently prevailing treatment – the protein PD1. We discovered a new protein, Ly6a, and found that its antibody eradicated tumors in our model animals - even those resistant to PD1 therapy. We are currently working to translate our findings into a drug for human cancer patients, hoping to offer an effective new treatment".

A new study from the Coller School of Management at Tel Aviv University sheds light for the first time on an important issue in the business world: employees withholding their inventions from the companies they work for. Although the law and/or employment contracts typically grant organizations the rights to their employees’ inventions, invention withholding is quite common. It carries serious implications for businesses, especially in knowledge-intensive industries. The study reveals alarming data: one out of every four employees in commercial organizations has withheld an invention from their employer at least once. In many cases, this withholding is done deliberately, with the intent to use the invention after leaving the organization. The research was led by Dr. Sarit Erez, in collaboration with Prof. Yaniv Shani and Prof. Abraham Carmeli from the Coller School of Management at Tel Aviv University. The study was published in the prominent journal Academy of Management Perspectives.

Dr. Erez explains: "Commercial organizations, particularly those in knowledge-intensive industries, encourage innovation among their employees, and their success largely depends on those employees coming up with groundbreaking inventions. To protect companies’ rights to these inventions, legal systems and standard employment contracts typically grant the employer ownership of inventions made by their employees, while requiring employees to disclose any invention they have come up with at work. This allows the employer to obtain patents and protect the invention. To increase employees’ motivation to disclose their inventions, many companies implement incentive systems, offering financial grants and/or recognition, such as badges of honor, to inventors. But at the end of the day, when an employee comes up with a new invention, they are faced with a behavioral dilemma: should they fulfill their legal obligation and disclose the invention to their employer, knowing they will lose ownership, or violate their obligation and hold on to the possibility of capitalizing on their invention outside the company? Indeed, it is a common scenario to see people leave one organization and either join another in the same field or even start their own company — often to develop an invention conceived in their previous workplace".

Video Credit: Dr. Sarit Erez.

Who Really Owns the Work You Create?

Dr. Erez continues: "These types of cases often end up in court, where an employer sues a former employee — or their new employer — alleging that they are using an invention that the employee conceived while working for them and that the patent rightfully belongs to the original employer. Having practiced law in the private sector for about 20 years, I often represented employees, employers, or employee organizations in disputes of this type. It became evident that the legal tools currently used to address this issue are not the most effective approach. I used to believe that management tools were designed to increase employees’ willingness to disclose their inventions and reduce their tendency to withhold them could be far more effective. But when I looked for academic research on this subject, I found only a handful, and even those focused mainly on the withholding of inventions in academia rather than in commercial organizations. It became clear to me that the issue of withholding inventions, which is so vital to the growth of knowledge-driven companies, had not yet been thoroughly explored in management strategy. With this study, we aimed to shed light on this important phenomenon and begin to address it from a business perspective".

For the study, the researchers distributed an anonymous online questionnaire, asking inventors to report whether they had ever withheld one or more inventions from their employers. Participants were also requested to describe the event, including its reasons and circumstances. A total of 199 valid responses were collected. Dr. Erez details the findings: "54 participants, or 27 percent of the respondents, reported withholding at least one invention from the organization in which they worked. Of these, 28 percent explicitly stated that they did so to develop the invention themselves after leaving the organization or bringing it as a sort of ‘dowry’ to their next employer. The others cited a variety of reasons, some psychological and some financial. These included an emotional attachment and sense of ownership over the invention as a personal creation; fear that someone else would take credit; conflict with their employer; lack of trust in management; dissatisfaction with pay; and the belief that they would not be adequately compensated for an invention that would profit the organization".

Changing the Work Culture

In the next phase, the researchers developed a unique and validated measurement scale, the first of its kind, to assess employees’ tendencies to either disclose or withhold inventions from their employers. The findings revealed that withholding or disclosing inventions are not simply opposite sides of the same behavior, but rather two fundamentally different behaviors: an employee might refrain from disclosing a certain invention for a variety of reasons (such as a heavy workload or the belief that the invention still requires development and is not ready to be disclosed). However, a deliberate and active decision to withhold an invention in order to prevent the transfer of ownership to the organization is a distinct behavior that may be influenced by completely different factors (for example, the employee’s feeling that they are poorly treated by the company regardless of the invention itself). Dr. Erez explains: “This distinction is extremely important for organizations seeking to address the problem. Actions taken by companies today, such as offering financial incentives or recognition to inventors, may encourage more disclosures to the organization. However, such measures may be less effective for employees who deliberately withhold a promising invention with the intention of using it further down the road, outside the organization”.

According to the researchers, this newly developed scale can serve as a foundation for further studies on the subject. Additionally, it can help employers build an effective innovation management strategy that minimizes the withholding of inventions within the organization.

Dr. Erez concludes: “In this study, we conducted an in-depth exploration of a widespread phenomenon that has long concerned legal professionals around the world, but so far has hardly been examined from a managerial perspective: employees in the business sector who withhold their inventions from the company that employs them. We urge researchers in academia to continue investigating this important topic, and call on employers to take notice: these behaviors exist, and it is crucial to address them. For our follow-up studies, we are developing management tools to help employers tackle the issue in all its complexity. We believe that with the right management strategies, it is possible to encourage disclosure and significantly reduce the withholding of inventions — preventing the need for legal battles down the line”.