Whose Lives? What Values? Herd Immunity, Lockdowns and Social/Physical Distancing

COVID-19 zugzwang: Potential public health moves towards population (herd) immunity

Have deaths from COVID-19 in Europe plateaued due to herd immunity?

Herd Immunity Not Possible in Long-Term Care

Objective: evaluate the incidence of diphtheria in Russia from the beginning of mass immunization of children to date and analysis of long-term studies of coverage of vaccination and the state of antitoxic antidiphtheria immunity of the population. Materials and methods. Presents the incidence of diphtheria in 1955 - 2016 and analysis of the condition of antidiphtheria antitoxic immunity of the population of Russia (2010 - 2016) according to seromonitoring of the 83 subjects of the Russian Federation. We examined 367 031 people, of which 65 557 children, 74 033 teenagers and 277 441 adults and examined 13 785 control of blood serum of indicator groups of 52 subjects of the Russian Federation (2 888 children, teenagers and adults 1 639 - 9 258 people) to assess the uality of seromonitoring in the subjects of the Russian Federation and the data associated with the level of previtali of the population. The level of antitoxic antidiphtheria immunity was determined using the reaction of passive hemagglutination antigen of the antigenic. The immunity level was evaluated by the content of medium and high titers of antibodies in serum. The aggregation of data in the work were used the methods of parametric statistics. Results and discussion. Before 1959, in Russia the incidence of iphtheria was very high - 68 0 - 93 0 per 100 thousand population Mass immunization of children was carried out only since 1959 (decree No. 323 «On the elimination of the incidence of diphtheria in the USSR», approved by the USSR health Ministry, 1959 June 23). After the introduction of the Order of the mass immunization of children since 1959, the incidence began to decline sharply - annually by 30 - 40%. In 1968, the incidence rate was 0.89 and in 1975 - 0.03. Total sick 51. However, from 1980 to 1985 marked rise in the incidence (0.2 - 0.9) were mostly ill adults, and since 1990 began a new expansion of morbidity. In 1994, the incidence rate was equal to 26.8 per 100 thousand population. Was 39 703 cases, died 1 104 people, of whom 254 of the child. according to the Ministry of health report the reason for the rise - sereznye deficiencies in the organization and conduct of immunization. After the mass immunization of the entire population in 1993 - 1995 the incidence began to decline after the 2nd booster vaccination in adults (2005) incidence rates were at the level of hundredths per 100 thousand population - 0.06 - -0.01 and in 2011 at the evel of thousandths - 0.006 - 0.001. Since 2009 was not registered fatal cases. The level of immunization of the population of the Russian Federation from 2005 - 2016. was consistently high in children, 96.6 - 97.1% among adolescents of 96.8 - 99.6% in adults in total and by age groups, consistent with the requirements of the who - 97.7 - 98.3%. Information on high levels of vaccination coverage are confirmed by the results of serological monitoring and data control studies of serum. In 2010 - 2015 in children antibody on the protective level was identified 95.2± 0.2% 97.0 ± 0.15% serum in high tension immunity (77.1 ± 0.37% 88.5 ± 0.3%); among teenagers - 97.6 ± 0.13% 98.2 ± 0.12% and 88.1 ± 0.26% - 91.0 ± 0.26%; in adults 91.1 ± 0.17% - 94.5 ± 0.19% and 74.1 ± 0.26% - 84.0 ± 0.18% respectively. By age group adults in Russia on average the condition of antidiphtheria immunity in all years was high at 96.6 ± 0.37% - 97.5% ± 0.17% and somewhat lower in older age groups - 88.0 ± 0.48% - 90.3 ± 0.43% (50 - 59, 60 years old and >). Data control studies of blood serum of children, teenagers and adults: 90.7 ± 0.89% 99.5 ± 0.5%; 92.2 ± 0.6% - 100% и 87.1 ± 1.03% 95.6 ± 0 . 64% respectively. Conclusion: long-time study of the condition of antidiphtheria immunity of the population and control studies of serum of indicator groups, allowed to estimate objectively high level of specific protection of the population against diphtheria. This has contributed to stabilizing the incidence at a sporadic level, with sporadic cases; no deaths and will continue to provide a favorable prognosis for diphtheria in the country

The public health benefits of herd immunity are often used as the justification for coercive vaccine policies. Yet, ‘herd immunity’ as a term has multiple referents, which can result in...

BackgroundPancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States with 5-year survival rates below 10%. PDAC is commonly diagnosed after metastasis has occurred...

Altered immune environment in peritoneal endometriotic lesions: relationship to lesion appearance

The necessary herd immunity blocking the transmission of an infectious agent in the population is established when the prevalence of protected individuals is higher than a critical value, called the herd immunity threshold. The establishment of herd immunity in the population can be determined using the vaccination coverage and seroepidemiological surveys. The vaccination coverage associated with herd immunity (Vc) can be determined from the herd immunity threshold and vaccine effectiveness. This method requires a vaccine-specific effectiveness evaluation, and it can be used only for the herd immunity assessment of vaccinated communities in which the infectious agent is not circulating. The prevalence of positive serological results associated with herd immunity can be determined from the herd immunity threshold, in terms of prevalence of antibodies (pc) and serological test performance. The herd immunity is established when the prevalence of antibodies is higher than pc. This method can be used to assess the establishment of herd immunity in different population groups, both when the infectious agent is circulating and when it is not possible to assess vaccine effectiveness. The herd immunity assessment in Catalonia, Spain, showed that the additional vaccination coverage required to establish herd immunity was 3–6% for measles, mump and varicella and 11% poliovirus type III in school children, 17–59% for diphtheria in youth and adults and 25–46% for persussis in school children, youth and adults.

To the Editor: To control the coronavirus disease 2019 (COVID-19) pandemic and reduce the complications and deaths resulting from the transmission of the disease, a variety of COVID-19 vaccines, such as mRNA vaccines, adenovirus-vector vaccines, inactivated viral vaccines, and others, have been licensed for emergency use. Most of these vaccines were rolled out in different countries following the successful completion of phase 3 clinical trials. Scale-up of vaccine production and vaccination have provided notable protection to large populations, although some vaccines may cause side effects. Furthermore, as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has mutated and spread further over time, some notable novel variants have emerged but whether these variants are vulnerable to currently available vaccines is yet to be determined. Despite the availability of vaccines across the world varies and some countries are still struggling to obtain vaccines and effectively store vaccines, a large proportion of people have now been vaccinated. An international consensus has been reached on the use of global mass vaccination to curb the epidemic. Remarkable achievements are demonstrated because the severity and mortality rate have decreased significantly compared with early 2020. Therefore, it is appropriate to evaluate and reassess the current epidemic situation and formulate timely plans to achieve herd immunity. To date, there have been 337 candidate COVID-19 vaccines that have been reported or registered worldwide [Supplementary Figure 1, https://links.lww.com/CM9/B390]. Of these, 142 are undergoing clinical development, while the rest of them are in preclinical trials. The protein subunit is the most commonly used platform, accounting for 33% of all vaccine candidates. Most current vaccines are on a two-dose schedule to achieve optimal immunity against SARS-CoV-2. Most candidates are administered by intramuscular injections. The mechanisms for how different vaccines act on the immune system are presented in Supplementary Figure 2, https://links.lww.com/CM9/B390. Based on the different production mechanisms, vaccines are mainly classified as inactivated vaccines, protein subunit vaccines, vector-based vaccines, mRNA-based vaccines and deoxyribonucleic acid (DNA) based vaccines, virus-like particle vaccines, and live-attenuated vaccines. According to World Health Organization (WHO), the vaccines procured the most are Comirnaty (Pfizer BioNTech, America-Germany), Spikevax (Moderna, America), Vaxzevria (AstraZeneca, Britain), Covishield (SII, India), and CoronaVac (Sinovac, China). The characteristics of the selected vaccines are listed and compared in Supplementary Table 1, https://links.lww.com/CM9/B390. Live-attenuated vaccines might possess a risk of viral infection and transmission. DNA vaccines in nucleic acid vaccines present the risk of oncogene activation, inactivation of tumor suppressor genes, accidental replications, or chromosomal instability due to the potential integration into the host genome. mRNA could bind to endosomal or the cytosol pattern recognition receptors before translation. Endosomal single-stranded or double-stranded ribonucleic acid (RNA) can be recognized by toll-like receptor 3, 7, and 8, while short and long filaments of double-stranded RNAs may be recognized by retinoic acid-inducible gene-I in the cytoplasm, as well as melanoma differentiation-associated protein 5. The subsequent activation of innate immunity can theoretically generate pro-inflammatory cascades, for instance, inflammasome formation and activation of the nuclear transcription factor-kappa B pathway.[1] This might lead to several potential adverse side effects or induce autoinflammatory or autoimmune conditions. Neutralizing antibodies generated from previous adenovirus infections might potentially prevent human cells from incorporating the adenovirus vector, or impact adenovirus vector vaccine safety by initiating an inappropriate immune response. Most adverse reactions occur during the window period after vaccination. Almost all anaphylactic reactions (injection site redness and swelling, fatigue, and fever) occurred within 15 to 30 min.[2] Therefore, 30 min is recommended as the observation period post-vaccination for those individuals at risk of allergic reactions. The incidence of adverse reactions from adenovirus and mRNA vaccines was higher than that of other vaccines. Severe adverse reactions were rarely seen in adults,[3] and the incidence rates of anaphylaxis and myocarditis were reported to be 2.5 to 4.8 billion and 6 to 27 billion for mRNA vaccines, respectively. Thrombosis with thrombocytopenia syndrome was reported as an adverse reaction for the AstraZeneca vaccine (2 billion), while for the Ad.26.COV2.S vaccine (Johnson & Johnson, USA), thrombosis with thrombocytopenia syndrome (3 million) and Guillain–Barré syndrome (7.8 million) were reported. Transverse myelitis (1 million) was reported for BNT162b2. Capillary leak syndrome and multisystem inflammatory syndrome were possible side reactions for AZD1222 (AstraZeneca, Britain). The major severe adverse reactions are summarized in Supplementary Table 1, https://links.lww.com/CM9/B390. SARS-CoV-2 vaccines have been developed in a relatively short time after the initial outbreak, using knowledge gained from SARS and Middle East respiratory syndrome vaccines. The Spike protein, a large transmembrane protein I that contains a receptor-binding domain (RBD), is a common antigen target in vaccine development. The RBD spike protein fragment, widely used in vaccine development, is considered highly antigenic and plays an important role in humoral and cellular immune responses. This protein also induces neutralizing antibodies that play an essential role in protective immunity by preventing host cell attachment and infection. Furthermore, when used in conjunction with S protein epitopes, conserved nucleocapsid (N) and membrane (M) proteins could synergically enhance immunogenicity, and T cell and cytokine release. At present, SARS-CoV-2 epitope vaccines based on polypeptide subunits include the adjuvant, cytotoxic T cells, helper T cells, and B-cell epitopes. Non-toxicity, non-sensitization, thermostability, and the capability to induce humoral and cell-mediated immunological reactions are advantages of these vaccines. The key to designing peptide vaccines is the recognition of B-cell and T-cell epitopes that are immunodominant for specific immune responses. Variants of the SARS-CoV-2 spike protein have been reported worldwide. The spike protein is highly glycosylated; therefore, new variants may have different infectivity and antigenicity. Newly emerging, fast-spreading variants of SARS-CoV-2 can also reduce the overall protective effects of vaccines. Based on the transmissibility, pathogenicity, and immunogenicity, significant variants are divided by the WHO into a "variant of concern (VOC)" and "variant of interest." There are currently five VOC mutants identified by the WHO: B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta), and B.1.1.529 (Omicron). As there have been many reports on the previous variants, including alpha, beta, and gamma, we focus on the current primary strain with high transmissibility. Former data are summarized in Supplementary Table 2, https://links.lww.com/CM9/B390. With up to 37 amino acid mutations on its S protein, the spike protein of the Omicron mutant exhibits a stronger binding ability to angiotensin-converting enzyme 2, which explains the potential mechanism underpinning its enhanced infectivity. Moreover, Omicron is believed to be associated with a higher risk of reinfection and a significantly enhanced immune escape ability, although the underlying mechanism remains unclear. As reported, the neutralization of the Omicron variant was undetectable in most vaccines, which may result from its ominous antigenic properties. The emergence of the Omicron variant has raised concern over the efficacy of neutralizing antibodies induced by COVID-19 vaccines as many vaccinated individuals have been infected with Omicron. Two BioNTech vaccinations, which provide more than 90% protection against serious Delta variant infection, may be significantly less effective against Omicron. Neutralizing antibodies against omicron were detectable in only about 20% to 24% recipients of BNT162b2,[4] and undetectable in all Coronavac recipients. The geometric mean neutralization antibody titers (GMT) against the Omicron variant in BNT162b2 recipients were significantly lower compared with Beta and Delta variants. Laboratory investigations suggest that Pfizer-BioNTech vaccines appear to offer better protection from the Omicron with a third dose as a booster, the latter of which increase the neutralizing antibody titers by 25-fold compared with the other two doses. Notwithstanding the low efficiency of the current vaccines against the novel variant, vaccines seem to have the potential to reduce the severity and death rate in individuals infected with omicron. The results about effectiveness of a few vaccines on omicron published on scientific journals are summarized in Supplementary Table 3, https://links.lww.com/CM9/B390. Herd immunity refers to the interrupted transmission of the disease in a biological population that occurs when most individuals have developed immunity to pathogens. There are two main ways to achieve herd immunity: natural infection (passive immunity) or vaccination (active immunity). Current studies estimate that the basic reproduction number (R0) of COVID-19 is 2.5 to 5.8 in different studies,[5] which translates to a predicted herd immunity threshold of between 60% and 83%. In clinical trials, the vaccine efficacy has been reported to be between 60% and 95%, depending on the vaccine. These calculations indicate that higher vaccination coverage may be needed to interrupt transmission. Ultimately, with the global population approaching 8 billion, 11 billion doses, depending on the type of vaccine, may be needed to stop transmission. It seems that it is no longer reasonable to obtain herd immunity from natural infection, as individuals became reinfected even though the positive rate of serum antibody is high after the first infection. Previous infections cannot protect individuals from the epidemic due to the constant mutations of the virus. It was estimated that 250,000 might result from the policy of natural herd immunity. Thus, many countries that used to develop herd immunity by the natural infection have now resorted to the weapon of vaccines. In a previous study, among the residents who received at least one dose of vaccine, there were 822 novel coronavirus cases (4.5% of the vaccinated residents) from 0 to 14 days and 250 cases (1.4%) from 15 to 28 days. The infection rate of residents vaccinated with two doses of vaccine decreased from 1.0% to 0.3%, while the rate in unvaccinated residents also decreased from 4.3% to 0.3%.[6] Moreover, most infected patients are asymptomatic cases, indicating that the vaccine can not only reduce the infection rate among unvaccinated residents, but also reduce the severity of infected cases, which is consistent with the effect of vaccines on different variants. The WHO has declared that it supports achieving herd immunity through vaccination, rather than by allowing the disease to spread through any segment of the population. Given the fact that the GMT after vaccination usually becomes lower with the emergence of novel variants such as Omicron, whether vaccination is a long-term approach to developing herd immunity remains to be seen. Sufficiency and efficiency are challenges to developing herd immunity, which may lead to dilemmas in vaccination. Due to the emergence of the Delta variant and the lack of vaccines, the government of England has changed the schedule from providing authorized two doses to one that gives priority to the first dose, and postponed the second dose from 3–4 weeks to 12 weeks. It seems that under the condition of limited resources, a single dose will save more lives. Conversely, a single dose may lead to more vaccine failures or introduce mutations resistant to the vaccine, known as vaccine escape. Another dilemma is the priority of the vaccination afforded to different segments of the population. A study found that giving priority to vaccinating older people can reduce the number of deaths and hospitalizations and save the most lives. However, Indonesia focused on working age adults rather than the elderly to reduce community transmission faster, as adults of working age tend to be exposed to the environment. Besides, the intention of vaccination plays an important part in herd immunity, which depends on regions, the efficiency, type, and side effects of vaccines. According to an anonymous cross-sectional survey, people in Australia (96.4%), China (95.3%), and Norway (95.3%) are more likely to receive COVID-19 vaccines, while people in Japan (34.6%), the U.S. (29.4%), and Iran (27.9%) are unwilling to receive vaccinations. Males, elders, and people with lower education levels seem to be more resistant to vaccination. Vaccines with an efficiency of more than 90% and fewer adverse reactions are more popular, and mRNA-based vaccines are mostly unpopular in countries from the Southeast Asia. The efficiency and adverse reactions are issues of greatest concern, which may shed light on the direction to herd immunity.[7] In conclusion, vaccines are an important tool to curb the pandemic. Post-licensing studies need to be systematically conducted to investigate the core parameters of herd immunity, as well as the subsequent formulation of policies. COVID-19 vaccines have been developed and released within 11 months after the initial outbreak. In the near future, large-population vaccination and prevention measures still need to be implanted, which would ensure equitable global opportunities for vaccination and ensure immunity to emerging strains of the virus. Funding This study was supported by grants from the Logistic Support Department of Central Military Commission Health Care Project (No. 21BJZ35) and National Natural Science Foundation of Beijing (No. 7212104). Conflicts of interest None.

Keywords:: antivaccinationistsasymptomaticCOVID-19fatalitiesherdimmunizationrinderpestsecond wavesmallpoxtransmission

Introduction Vaccination is the most effective method of protecting people from invasive meningococcal disease (IMD). Of all the capsular groups, B is the most common cause of invasive meningococcal disease in many parts of the world. Despite this, adolescent meningococcal B vaccine programs have not been implemented globally, partly due to the lack of evidence for herd immunity afforded by meningococcal B vaccines. Areas covered This review aims to synthesize the available evidence on recombinant 4 CMenB vaccines’ ability to reduce pharyngeal carriage and therefore provide indirect (herd) immunity against IMD. Expert opinion There is some evidence that the 4CMenB vaccine may induce cross-protection against non-B carriage of meningococci. However, the overall body of evidence does not support a clinically significant reduction in carriage of disease-associated or group B meningococci following 4CMenB vaccination. No additional cost-benefit from herd immunity effects should be included when modeling the cost-effectiveness of 4CMenB vaccine programs against group B IMD. 4CMenB immunization programs should focus on direct (individual) protection for groups at greatest risk of meningococcal disease. Future meningococcal B and combination vaccines being developed should consider the impact of the vaccine on carriage as part of their clinical evaluation.

Prevention of metastases is critical for the future of breast cancer research, as metastatic cancer is extremely difficult to manage and treat. Solid tumors often contain patches of hypoxic regions that yield aggressive, pro-metastatic phenotypes. Recent work in our lab has shown that long-term hypoxia suppresses type I interferon (IFN) signaling in breast cancer cells, and this suppression of IFN signaling is maintained even after reoxygenation, indicative of “hypoxic memory.” Breast cancer cells and circulating tumor cells (CTCs) that have exited hypoxia but maintain such hypoxic memory showed enhanced metastatic potential. In addition to tumor intrinsic effects, IFN suppression can dampen surrounding immune cell populations within the tumor microenvironment, primarily through interferon-stimulated genes (ISGs) which carry out immune functions through activation of various immune cell populations. More research is needed to understand how ISGs are downregulated in hypoxia and how those changes in gene expression contribute to immunosuppressive ability of hypoxic and post-hypoxic cells. Interferon-inducible 44-like (IFI44L) is an ISG that has been associated with tumor-infiltrating lymphocytes and enhanced metastasis in other cancers, but its role in breast cancer has not been studied. We found that IFI44L is significantly suppressed in breast cancer cells in hypoxia and maintained after reoxygenation as hypoxic memory. Overexpressing interferon regulatory factors (IRFs), which are positive regulators of the type I IFN pathway, did not rescue hypoxic suppression and memory of IFI44L, suggesting IRFs are not the sole regulator of IFN and ISG expression in hypoxia. Current experiments in the lab are ongoing to address the mechanisms responsible for hypoxic memory of IFI44L suppression. Additionally, co-culture studies of IFI44L knockdown and overexpression breast cancer cell lines with different immune populations will shed light on the role of hypoxic suppression of IFI44L in immune evasion. To better understand implications of maintained IFI44L suppression, we will also examine immune cell activity and metastatic potential using in vivo mouse studies. We expect to see less immune cell effect and enhanced metastasis with IFI44L knockdown and reversed phenotypes with overexpression of IFI44L. Understanding mechanisms of immune suppression and evasion mediated via IFI44L can lead to strategies for targeting hypoxia-mediated tumorigenesis and metastasis. Citation Format: Rebecca Marker, Aidan Moriarty, Remi Klotz, Min Yu. Mechanisms mediating hypoxic memory of type I IFN signaling suppression and implications for immune evasion in luminal breast cancer cells [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A062.

Background Vedolizumab is one of the current treatments for patients with Inflammatory Bowel Disease (IBD). The efficacy and safety, together with its gut specificity, make this drug an appealing therapeutic option for IBD patients with moderate to severe disease. However, as observed for other biologic treatments, a significant proportion of patients do not have an initial response to vedolizumab treatment. Currently, there is a lack of reliable biomarkers for vedolizumab treatment response, although this would help to palliate the socioeconomic costs derived from this disease. For that reason, the primary aim of this study is to establish the basis for the search of transcriptional factors associated with vedolizumab treatment response. Methods For the realization of this study, we collected blood samples from responder and non-responder Ulcerative Colitis (UC) patients treated with vedolizumab. The clinical response was measured using the Partial Mayo Score. The frequencies of different immune system populations were analysed by flow cytometry. Moreover, we measured the transcriptional levels of several genes in peripheral blood mononuclear cells (PBMC) by RT-qPCR. These experimental procedures were performed at baseline (T0) and after 14 weeks of follow-up (T14). Results We enrolled nine patients with an average age of 46.25±11.71, of which seven were previously treated with anti-TNF therapy. Our results show a specific pattern in responder and non-responder patients in the percentages of different innate and adaptive immune cell populations at T0 versus T14. Similarly, we observed a significant reduction in the expression of some chemokines (i.e., CCL25) and pro-resolutive factors (i.e., ANNEXIN A1) at T14 versus T0 in PBMCs from vedolizumab responder patients, which was not observed in non-responder patients. Conclusion Our data suggest that the frequencies of certain immune populations are associated with the response to vedolizumab treatment. In the same way, we found that specific transcripts are modulated in response to this α4β7 integrin antibodies in PBMCs. Therefore, we found a solid system to search for vedolizumab therapy response markers using low invasive techniques.

Comprehensive characterization of the tumor and tumor microenvironment (TME) can improve our understanding of tumor progression and treatment outcomes. For example, quantification of the immune infiltrate can inform mechanisms of immune escape and predict response to checkpoint blockade. Standard experimental approaches exist to enumerate tumor-infiltrating immune cells, but they can have practical limitations of throughput, number of markers, or sample requirements. RNA sequencing can be used as a scalable solution to comprehensively profile the immune cell composition of the TME. However, care must be taken to ensure that the computational analysis accurately reflects the underlying immune cell composition. To address these challenges, we developed ImmunoID NeXT, an augmented, immuno-oncology-optimized exome/transcriptome platform designed to provide comprehensive information regarding the tumor and TME from a single FFPE tumor sample. This includes the quantification of tumor-infiltrating immune cells using RNA-seq analysis, which we compare to quantification by orthogonal methods. To generate our reference data, we profiled the transcriptomes of eight purified immune cell types using ImmunoID NeXT. Then, we analyzed multiple sample types and orthogonally quantified immune cells in each. These include profiling of healthy donor PBMCs with cytometry by time of flight (CyTOF), and immunofluorescence (IF) characterization of FFPE tumor samples. We also used ImmunoID NeXT to profile the immune infiltrate of over 500 tumor samples across 13 cancer types. Finally, we created a set of in vitro cell mixtures and profiled them by flow cytometry. We utilized the transcriptome profiles of eight purified immune cell types to develop reference expression signatures specific for each cell type. Then, we compared ImmunoID NeXT's transcriptome-based approach to CyTOF results of healthy donor PBMCs, showing accuracy in real samples with diverse immune populations. We also compared to FFPE tumor samples with IF, ensuring that our approach is able to profile the immune composition in tumor samples. Next, we highlight the diversity of immune populations across cancer types by applying ImmunoID NeXT to over 500 tumor samples. Finally, to demonstrate concordance across the eight cell types, we compared to flow cytometry results of in vitro cell mixtures. Analysis of the immune infiltrate of tumor samples can add to our understanding of the tumor-immune interaction, with potential applications including studies of response to immunotherapy. RNA sequencing can be utilized as a scalable approach for such analysis. Here, we test the accuracy of our approach using multiple sample sets with orthogonal profiling. We demonstrate that ImmunoID NeXT can accurately evaluate the composition of infiltrating immune cells in tumor samples. Citation Format: Eric Levy, Pamela Milani, Charles W. Abbott, Manxia Lee, Robert Power, John West, Richard Chen, Sean M. Boyle. Quantification of tumor-infiltrating immune cell populations with an augmented transcriptome [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4430.

The immune response to acute hypoxemia may play a critical role in high‐altitude acclimatization and adaptation. However, if not properly controlled, hypoxemia‐induced inflammation may exacerbate high‐altitude pathologies, such as acute mountain sickness (AMS), or other hypoxia‐related clinical conditions. Several studies report changes in immune cell subsets at high altitude. However, the mechanisms underlying these changes, and if these alterations are beneficial or maladaptive, remains unknown. To address this, we performed multiparameter flow cytometry on peripheral blood mononuclear cells (PBMCs) collected throughout 3 days of high‐altitude acclimatization in healthy sea‐level residents (n = 20). Additionally, we conducted in vitro stimulation assays to test if high‐altitude hypoxia exposure influences responses of immune cells to subsequent inflammatory stimuli. We found several immune populations were altered at high altitude, including monocytes, T cells, and B cells. Some changes in immune cell populations are potentially correlated with AMS incidence and severity. In vitro high‐altitude PBMC cultures stimulated with lipopolysaccharide (LPS) showed no changes in pro‐inflammatory cytokine production after 1 day at high‐altitude. However, by day three pro‐inflammatory cytokine production in response to LPS decreased significantly. These results indicate that high‐altitude exposure may initiate an inflammatory response that encompasses innate immune sensitization, with adaptive immune suppression following acclimatization.