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Immuno-Colombia: Overview of immunotherapyImmuno-Colombia: Checkpoint Blockade-based Therapies (Part 1)Immuno-Colombia: Checkpoint Blockade-based Therapies (Part 2)Immuno-Colombia: Anti-cytokine therapies (Part 1)Immuno-Colombia: Anti-cytokine therapies (Part 2)Immuno-Colombia: Tumour infiltrating lymphocyte therapy (Part 1)Immuno-Colombia: Tumour infiltrating lymphocyte therapy (Part 2)Immuno-Colombia: MDSCs promote tumour growth and escapeImmuno-Colombia: Therapeutic cancer vaccinesCourse EvaluationsCourse Evaluations by the students were very positive. On a scale of 1-10, the students ranked 9.2the five questions related to the course, its methodology and the quality of the Faculty and theirpresentations.Students, do you think thatthe course covered the topic sufficiently?9.3the new online format was appropriate to achieve its goals?9.2the themes of the course were sufficiently addressed?9.4the selection of the faculty was appropriate?9.7the level of the presentations by the faculty was appropriate?9.6n 350246810Score SDTo the question: “Overall, do you think that this event has met your expectation and is worthrepeating? If yes - what would you like to see different next time? If no - list one reason”, thefollowing are some representative answers:“Yes, I loved meeting people from all over the world and getting to work with them and learna lot of new things that I'm sure I will apply in my professional career.”“It was amazing! I just hope next time can be presential.”“Yes, I would like to interact more with the Faculty in a later opportunity.”“Yes, I really like the course. It was very interesting, and I don't have any suggestion. It met allmy expectations and more.”“Yes, I think it was really helpful as an update of information and knowledge in the immunooncology field. I would repeat the 2 weeks panel of talks and discussion session. However, Idid not appreciate the pre-course since it was too basic for people already working on (andsome of us even teaching) immunology.”

“Yes, this course was a wonderful experience and I think it is worth repeating it. May be fornext time it would be interested if we could have more exercises regarding theoreticalcontents on each sub-topic. May be online games, or any other pedagogic strategies besidesmultiple-choice questions.”“Yes. The evaluation must be more democratic. Students should see the google drive used.”“Yes, of course. I liked all the presentations by the Faculty. Maybe, the next time, you couldtalk about new topics - nanomedicine and cancer immunotherapy.”RESEARCH PROJECT PREPARATION AND PRESENTATIONNine groups of 5-6 students/group were set up by ML and RP, taking care that each group includedstudents from different countries, diverse research background and gender equity, and assigned toa Faculty/Mentor who had previously defined a question to be developed in a research project. OnApril 16th, the Mentors met with their respective group to explain the significance of the researchquestion and give them instructions on how to approach it. The students decided how they wouldwork and meet virtually and possible future meetings with the Mentor. On May 7th, during the finalsession, all the groups had 10 min to present the Project, using the same template. Presentationswere followed by questions and comments by the Faculty. The following are the research projectsdeveloped by the students:1. Defining the role of conventional dendritic cell 1 (cDC1) in anti-tumor immunity. DanielaRomina Montagna, Rajesh Kumar Gupta, Karen Dayanna Alvarez-Diaz, Gerardo Corral-Ruiz,Jeremias Dutto, Mouna Khan. (Carla Rothlin, Mentor)2. Assess predictive markers for differentiating checkpoint inhibitor resistance patients fromcheckpoint inhibitor responsive patients. Sarai Gisel De León-Rodríguez, Salma Abdeljalil,Lucia Boffelli, Wilbert Mbuya, Xiao-Hua Luo. (Betsy Quackenbush, Mentor)3. Can the in vitro growth and effector function of human γδ T-cells be enhanced by STINGinnate receptor ligands? Jessica Mariel Sierra, Moulay Yassine Belghali, Cecilia Smith, CintiaKaufman, Ulrich Femoe Membe (Dieter Kabelitz, Mentor)4. How to prevent CAR-T cells from becoming dysfunctional? Isadora Ferraz-Semionatto, JuanCarlos Nuñez-Enriquez, Dennis Dogbey, Valeria Sandoval-Torres, Akiko Suzuki, MacarenaMamberto. (Sonia Guedan, Mentor)5. Knowing the importance of monocytes in the pathogenesis of lupus nephritis, design animmunotherapy for lupus kidney disease. Zeineb Zian, Gisela Maria Suarez-Formigo, ImaneZouane, Ichrak Bannour, Cinthia Olexen. (Gloria Vásquez, Mentor)6. How could TIL therapy be further enhanced to achieve specificity and resistance to theimmunosuppressive tumor microenvironment (while keeping a reasonablemanufacturing period)? Carlos Orozco, Sawsan Feki, David Rosso, Yuliana Andrea OsorioOsorno, Nadia Bannoud, Mariem Tira (Soraya Zorro, Mentor)

7. Develop a panel of tests based on MDSC that will identify patients at high risk fordeveloping severe COVID-19. Aldana Trotta, Rubí Esmeralda Romo-Rodríguez, IkramHammi, Anna Ritah Namuganga, Camila Agustina Bach. (Augusto Ochoa, Mentor)8. Improving a response to a cancer vaccine. Jesús Guzmán-Mendoza, Juan Manuel OrtizWilczyñski, Doudou Georges Massar Niang, Micaela Belén Quereda-Corso, Carla SanzochiFogolin, Uzochukwu Ukachukwu (Olivera Finn, Mentor)9. Design a blood test for early breast cancer detection using liquid biopsy markers.Mohamed El-Hadi Seninet, Jocelyn Carolina Perez-Lara, Imtiyaz Ahmad Bhat, Karen Toledo,Olga Liliana Guzmán. (Klaus Pantel, Mentor).The projects were scored by the Faculty, with the exception of their own Project, and the twohighest scoring groups were selected as winners. Project #4 won the first prize, and Project #8 thesecond prize. The first prize will award each student with US 1000 and the second with US 500,towards attending any IUIS scientific meeting within the next two years, or to contribute to visitinga foreign lab for a short stay.The students also evaluated this part of the course, particularly the role of the Mentors and theexperience of virtual meetings with fellows from all over the world to prepare a research project.Their answers were very positive, 9.5, for both aspects. Interestingly, the number of virtualmeetings done to prepare the Project had a great variation (3 to 13) amongst groups, with anaverage of 6 meetings/group within the 3-week period.The students opinion of the projectHow well the mentor explained the project and answered questions?9.5How well did your group work?9.6How well did the group sessions work?9.5How many sessions did you have?9.5Did you enjoy the session with the presentations by all groups and the judging?n 350246810 12 14Score SDAlthough a good number of students felt nervous presenting in English, all of them agreed that itwas a positive experience and that the Zoom platform was a very nice tool for these kinds ofacademic activities. Some illustrative comments to the question “Was the research project part ofthe course helpful to you as a young scientist? Please explain.”, are the following:“yes! I have never made a research proposal from scratch, so it was really cool getting todesign all the rationale, hypothesis, experimental methods, etc. It was a great exercise forme!”“It makes me been outside of my comfort zone, I learned a lot.”“Yes, it allows the deliberate thinking to solve a particular within a short pace of time.”

“Yes, it made me look for literature and possible technics I didn't know, so I acquired newbackground and I'm aware of new tools now.”“Yes, it encouraged me that my Mentor had taken the time to correct and guide us.”“Yes, because I learn how to do team work internationally, and learn from many mistakes tooas comparing my work to others. That make me improve my presentations and speech, andmy speed of work.”“It was very useful. I have never created a research project. It was so challenging because itwas a new topic and a very new and innovative approach. For me was amazing!”“Definitely. Our Mentor really discussed the ideas for the project, and we were also able toask about possibilities to apply some of the ideas in our own projects.”“I really like the activity, and I think that this type of activity is quite helpful to train ourselvesin how to face a project in a collaborative way. Although we had some problems as a group,and not all the people were really committed to the assigned work, I learned many things.And our tutor was very predisposed to help us.”“Yes! The experience of working with colleagues from other countries and all thebrainstorming we did was an amazing and life changing opportunity. Even online, I feel reallyhonored to work with my group, everyone was really great, and I feel like we came up withan excellent Project.”“Very helpful. I learned a lot from the team. They stimulate me to learn.”“Yes. I learned about various treatment options on the subject. Promoted a scientific andfriendly relationship with the group members.”“Yes, we have learned how to build a project as a team. Also, we learned how to share ourideas, to discuss them and to decide together. On other hand, since each member of the teamhave specific skills, we all have learned from one and others.”“yes, it was a great idea because it makes me revisit the recorded sessions, improve thebibliography and it allows me to network actively with students from other parts of theworld.”“Yes, Absolutely. It was an amazing experience. I met other scientists with excellent ideas,very enthusiastic, and brilliant. We discussed our different point of view and we put to proofour skills to write a project. We shared part of our cultures and this is extremely enriched.Thank you for the opportunity.”“Yes, especially the challenge of working in group with different people, and having tocommunicate with everyone, and to come up with a project together, all of this will certainlyhelp me in the future.”Together, all opinions emphasized the importance of networking, exchange ideas and cultures.Nowadays that science is an international enterprise, this kind of exercises for young scientists is ofcapital importance.

FACULTY EVALUATION OF THE COURSEFacultyHow did you find lecturing on Zoom?Were the guidelines and plans/programme for the meeting clear?Did you find the discussion with the students engaging enough?Was the organization of the research project effective?0246810Score (mean)Faculty evaluation shows that they positively valued the organization of the course and the role ofthe moderators. Their comments were very positive on the importance of these activities. Not allthe Faculty felt comfortable lecturing by zoom, which may explain why some of them did not findeasy to engage in the discussion with the students.GENERAL CONCLUSIONS AND RECOMMENDATIONS BY THE ORGANIZING COMMITTEE1- The theme of the course was timely and important. Understanding immunotherapy requiresa good knowledge of all basic immunological phenomena, as well the immunopathogenesisof the target diseases.2- The on-line modality of the course was a big organizational challenge; however, theOrganizing Committee thinks that it was a successful course both in its scientific aspects aswell in that it allowed to have students and Faculty from many countries, at very differenttimes of the day and latitudes; something unthinkable under other modalities.3- Science, and Immunology in particular, is an international Enterprise, thus for youngimmunologists to have the opportunity to interact with other young fellows working incountries with different cultures and languages, but with the same life expectancies inscience, is a lifetime fascinating experience, as expressed by most of them in theircomments.4- The pre-course is the activity that needs more attention. The students have different levelsof immunology background. For students with a good immunologic background it may notbe necessary to spend time in reviewing the basic modules of the pre-course. It could bethat by testing their knowledge in an exam or just assessing their qualifications, theapplicants could be stratified, and the organizers decide who must go through the basicmodules.5- Although the traditional face-to-face courses offer the possibility of personal interactionsamong students and Faculty, and to have, for example, hands on laboratory workshops, theon-line courses allow to meet students and Faculty from different countries that otherwisewould not have the possibility to know each other. Also, for the Faculty, many have verybusy agendas, it is easier to accept an invitation to an on-line course than to travel forseveral days to a faraway place.

6- The experience gathered by IMMUNOPAEDIA, giving the technical support in all phases ofthe course is invaluable, as demonstrated in the present course; and, for sure, this coursealso helped the IMMUNOPAEDIA team to further strengthen their contribution.7- On-line courses facilitate the participation of organizers from different countries andfederations, not only from the organizing country, adding knowledge and experience tothem.8- Last but not least, the cost of on-line courses is much less than traditional on-site courses.

Appendix 1: ReportsImmuno-Colombia: Overview of immunotherapyProfessor Rothlin began by giving a brief history of cancer immunotherapy, starting with thefirst documented description of the tumour immune infiltrate by Virchow in 1863. She thenhighlighted the discovery of Coley’s toxin, a combination of heat-killed streptococcal bacterium andSerratia marcescens, in 1898 that William Coley used to treat malignant tumours. However,immunotherapeutic use of Coley's toxin was discontinued due to limitations such as no standardisedprotocol for the production and administration of Coley‘s toxin, and induction of heterogeneousimmune responses that did not always lead to anti-tumour immunity. These keys factors and theidentification of immune cells over the last century have enabled the development of many cancerimmunotherapies that target specific immune cell functions.Dr Rothlin presented data showing that administration of anti-CTLA-4 in mice after injection of51 Blim-10 tumour cells induced a reduction of tumour size and was associated with robust tumourcontrol. This study illustrated that T cells are a potential target for anti-tumour therapy. Additionally,research led by Gordon Freeman and Tasuku Honjo showed the critical role of inhibition of PD-1 byits ligands, PDL1 and PDL2, results in the negative regulation of T cells responses in cancerimmunotherapy. However, the main inconvenience with using these T cell response inhibitors is thehigh heterogenicity in their ability to control tumour growth.Professor Rothlin also highlighted two limitations of the cancer immunotherapy involving T cellscheckpoint blockade: In cancers relatively responsive to T cell checkpoint blockade (Melanoma, renal, lung andbladder cancer), treatment is only effective in a subset of patients Some types of cancer, such as pancreatic, prostate or brain tumours, are unresponsive totreatment.Other immunotherapies currently being tested target dendritic cells and macrophages usingimmune checkpoint inhibitors such as TYRO3, AXL and MERTK. Professor Rothlin presented datafrom her research group that showed that tumour infiltrating macrophages in YUMM 1.7 (YaleUniversity Melanoma model) and MC38 (colorectal cancer) models express MERTK. She thendemonstrated that MERTK ablation significantly improved the survival of MC38 mice by limitingtumour growth but not of YUMM 1.7 mice. Differences in response rates between the two cancermodels were attributed to (i) the low level of inflammatory macrophages and (ii) lower proportionsof proliferating monocytes and Batf3 dendritic cells in the YUMM 1.7 murine model compared withthe MC38 model. Thus, demonstrating that anti-tumour immunotherapy based on MERTK inhibitionis not effective against all cancer types. These data further highlight one of the major limitations ofcurrent anti-tumour immunotherapies. She also provided evidence that demonstrated that CD8 Tcells are required for a successful anti-tumour response, while CD4 T cells are dispensable.Finally, Professor Rothlin presented research on the use of Sitravatinib (from MIRATItherapeutics), a pharmacological inhibitor of MERTK, alone or in combination with α-PD1 in theMC38 tumour murine model. She showed that Sitravatinib alone or in combination with α-PD1significantly improves survival in the MC38 tumour model.

Interested in a detailed introduction to cancer immunotherapy? Read advanced pre-coursematerial on Overview of Immunotherapy.Full lecture recording available at IUIS-ALACI-ACAAI Immuno-Colombia 2021 Lecture week1.Article by Ulrich Femoe MembeImmuno-Colombia: Checkpoint Blockade-based TherapiesImmunotherapy has revolutionised the treatment of oncologic malignancies. Immunecheckpoint inhibitors represent a new class of immunotherapy drugs. Professor ElizabethQuackenbush began her talk by introducing the importance of anti-cancer immune response inprotecting the host against primary tumour development or enhancing tumour escape. This processis tightly regulated by immune checkpoints, immune-cell molecules that function as inhibitors(“brakes”) of ongoing immune responses. Checkpoints are usually surface receptors that controleither the activation or the inhibition of immune responses. Checkpoint inhibitors that block thecheckpoints can restore the body’s anti-cancer mechanisms (e.g. anti-tumour T cells remainactivated). Approved checkpoint inhibitors have transformed the cancer treatment landscape andimproved the long-term outlook for many patients with late-stage metastatic cancer. But, becauseof resistance mechanisms, only 25% of patients have positive responses to checkpoint inhibitors.Dr Quackenbush then described the cancer immunity cycle leading to the accumulation ofimmune-stimulatory factors that can amplify and broaden T cell responses. This cycle is divided intoseven major steps (Figure 1), starting with the release of antigens from the cancer cell and endingwith the killing of cancer cells. Professor Quackenbush added that researchers should be aware thatT cells trafficking in the blood vessels (step 4) does not always reflect the reality in the tumour (step5). Thus, biomarkers based on immune profiling of blood cells and not the tumourmicroenvironment could lead you down the wrong rabbit hole.Each step of the cancer-immunity cycle requires the coordination of numerous factors, bothstimulatory and inhibitory in nature. Immune checkpoint proteins, such as CTLA-4, can inhibit thedevelopment of an active immune response by acting primarily at the level of T cell developmentand proliferation (step 3; Figure 1). We distinguish these from immune rheostat (“immunostat”)factors, such as PD-L1 (expressed by activated T cells), which can have an inhibitory function thatprimarily acts to modulate active immune responses in the tumour microenvironment (step 7).Blocking the binding of PD-L1 to PD-1 (Nivolumab and others) with an immune checkpoint inhibitor(anti-PD-L1 or anti-PD-1) allows the T cells to kill tumour cells.Dr Quackenbush then reported on the various checkpoint inhibitors currently used and indevelopment. She discussed the antibody protein targets, binding affinities and thepharmacokinetics measured in various tumour types. She also highlighted new developments andmethods to optimize delivery and efficacy in the field of checkpoint inhibitors, including nonfucosylation, pro-drug formations, bi-specific antibodies, and newer small molecules and peptidecheckpoint inhibitors to have better oral bioavailability, fewer immune-rel

COLOMBIAN ORGANIZERS INTERNATIONAL ORGANIZERS Luis F. García Member, IUIS EDU Committee Universidad de Antioquia, Medellín, Colombia Dieter Kabelitz Chair, IUIS EDU Committee University of Kiel, Kiel, Germany Gloria Vásquez Universidad de Antioquia, Medellín, Colombia Michelle Letarte Past-Chair IUIS EDU Committee Sick kids Hospital & University of Toronto, Toronto, Canada Gloria I .