Use Of Immune Checkpoint Inhibitor Therapy Research Articles

Examining the Application of Immune Checkpoint Inhibitors in Cancer Immunotherapeutic: A Systematic Review

To define the clinical utilizations, effectiveness, and challenges of immune checkpoint inhibitors (ICIs) in cancer treatments. A systematic review of the literatures regarding the efficacy of ICI therapy in the management of advanced melanoma, non-small cell lung cancer (NSCLC), and hepatocellular carcinoma (HCC) was performed. The effectiveness and safety profile of anti-PD-1 (Nivolumab, Pembrolizumab, and Cemiplimab /PD-L1 (Atezolizumab, Durvalumab, and Avelumab), anti-CTLA-4 (Ipilimumab) drugs were measured and evaluated in several clinical trials via treatment-related indicators (response rate, survival rate, progression-free survival, overall survival, median overall survival, and treatment-related adverse events). Considering the increasing use of ICI therapy in days to come due to its great potential, this review can be valuable in assisting professional students or even oncologists to have a general overview of the role of ICIs in cancer immunotherapeutic, particularly targets the advanced melanoma, NSCLC, and HCC.

Osimertinib tolerance in a patient with Stevens Johnson syndrome during osimertinib therapy after treatment with pembrolizumab

BackgroundOsimertinib has emerged as an important tool in the treatment of non-small cell lung cancers (NSCLC) with certain activating mutations of epidermal growth factor receptor (EGFR). However, Osimertinib may cause adverse effects, including severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The risk of certain adverse effects may be increased in the setting of recent use of immune checkpoint inhibitor (ICI) therapy, although it is unclear whether recent use of ICI therapy is a risk factor for Osimertinib-induced SJS specifically.Case presentationWe present a patient with EGFR L858R mutation-positive metastatic NSCLC who developed Osimertinib-induced SJS after recent administration of eight cycles of a pembrolizumab-containing chemotherapy regimen. Osimertinib, which was the best treatment targeting his lung cancer, was avoided due to history of SJS. Four years later, because of unresponsiveness or side effects of alternative treatments, he underwent Osimertinib challenge and tolerated it.ConclusionThis case highlights the importance of multi-disciplinary care and supports the hypothesis that the risk of SJS to Osimertinib is significantly higher in the context of recent administration of ICI therapy and, patients may tolerate Osimertinib after certain time has elapsed after the last dose of ICI.

The Most Effective Self-Sustaining Antitumor Responses Activated by anti-PD1 Antibody are Likely Mediated by PD1-Negative T Cells

Immune checkpoint inhibitor (ICI) therapy has transformed the battlefield of cancer therapy by showing some of the most dramatic and durable antitumor responses ever seen. Yet ICI therapy is only effective in a minority of cancer patients. Among responders, only a few of them demonstrated a durable and self-sustaining pattern of response. It would be desirable to repeat the most durable success of ICI therapy in as more cancer patients as possible. That requires the true understanding of the mechanism behind the therapy. In previous publication, we have pointed out that the current blocking model of how ICI therapy works is wrong in that it cannot explain some critical observations such as the trigger effect, the hyper-progression and the autoimmunity associated with the therapy. On the other hand, we have raised an alternative model based on the partial depletion of PD1-positive T cells and the subsequent homeostatic activation of remaining T cells. This model, which we call the depletion model, could explains all of the perplexing clinical observations mentioned above. It also predicts that under repeated administration of antibodies to PD1/PDL1, a common practice in the clinic, the surviving immune response must be mediated by PD1-nagative T cells. Since some of the most dramatic and durable responses to ICI therapy did not require antigen-releasing treatments (such a chemotherapy), they must be self-sustaining as well. Here, using real-world cases, we present evidence that the most effective and self-sustaining antitumor responses are likely mediated by PD1-nagative T cells, an observation supporting our depletion model for ICI therapy. This observation raises fundamental questions regarding the current clinical use of ICI therapy and points to a future direction for the search of ways to activate PD1-nagative T cells for antitumor response.

PSAT342 Hypothyroidism After Use Of Immune Checkpoint Inhibitor Therapy In Patient With Graves’ Disease

Abstract Background Immune checkpoint inhibitors (ICIs) are commonly used for many cancers. Thyroid gland involvement is the commonest endocrine toxicity seen with this class of drugs. Most common thyroid dysfunction is thyroiditis followed by hypothyroidism with some cases of recovery. There are rare case reports of Graves’ disease induced by ICIs. However, we report a patient with pre-existing Graves’ disease who developed hypothyroidism after immunotherapy. Clinical Case 66-year-old man with metastatic squamous cell carcinoma of lung was referred to endocrine clinic for suppressed TSH. He was diagnosed with metastatic poorly differentiated lung cancer in September 2018. He received cheamotherapy with carboplatin and paclitaxel from October 2018 to January 2019. He was switched to immune checkpoint inhibitors with programmed cell death protein-1 (PD-1) inhibitor pembrolizumab every 3 weeks from February 2019. ICI therapy was stopped in until July 2019 due to immune mediated hepatitis. He was started on high dose steroids. Lung cancer findings remained stable even after stopping ICIs. Prior to starting ICIs his thyroid functions were consistent with hyperthyroidism. He continued to have suppressed TSH until his 6th cycle of pembrolizumab. TSH was found be significantly elevated prior to his 7th infusion. He was referred to endocrinology for further management. Clinically, patient was asymptomatic except for fatigue. Family history was positive for mother with Graves’ disease. Laboratory results on presentation showed significantly elevated TSH, low thyroxine (T4) and triiodothyronine (T3) consistent with diagnosis of primary hypothyroidism. Thyroid stimulating immunoglobulin (TSI) was positive suggesting autoimmune thyroid disease. Thyroid scan showed decreased 24-hour uptake (0.8%). A diagnosis of immune checkpoint inhibitor (ICI) related hypothyroidism was made. He was started on hormonal replacement with levothyroxine 50 mcg daily. Review of previous thyroid blood tests showed suppressed TSH since October 2016, but he was never treated. Thyroid peroxidase (TPO) antibodies were positive in the past. Thyroid sonogram in December 2016 showed a heterogeneous thyroid with no nodules. A radioactive scan in 1/2017 showed normal 24-hour uptake (12%) with no hot or cold nodules. (Fig 1). Since starting levothyroxine, the dose has been adjusted few times and patient has been doing well. Conclusion This is a unique case of patient with Graves’ disease who was cured because of immune related adverse event from use of immune-checkpoint inhibitor therapy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Corneal Transplant Rejections in Patients Receiving Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) are antibodies that target and block immune checkpoints. These biologics were initially approved by the United States Food and Drug Administration (US FDA) in 2011 for the management of melanoma. Since then, the use of ICI therapy has increased, with many new medications on the market that treat approximately 50 types of cancers. Patients receiving this therapy are at an increased risk for transplant rejection, including corneal rejection. Ophthalmologists must be aware of individuals receiving ICI therapy as it may be a relative contraindication for patients with a history of corneal transplantation. Patients on ICIs may also experience ocular side effects, including uveitis, dry eye, and inflammation, while on checkpoint inhibitor therapy. This commentary discusses the current understanding of immune checkpoint inhibitors, their mechanism of action, their ocular side effects, and their role in corneal transplant rejection.

Updates on Immunotherapy and Immune Landscape in Renal Clear Cell Carcinoma.

Simple SummaryClear cell renal cell carcinomas (ccRCC) have several distinct immunological features, including a high degree of immune infiltration and relatively low mutational burdens, the resistance to cytotoxic chemotherapy, and relative sensitivity to anti-angiogenic therapy and immunotherapies. Immune checkpoint inhibitor (ICI) therapy has become standard care in the treatment of ccRCC, but a better understanding of the molecular and cellular characteristics of ccRCC is needed to truly optimize the use of ICI therapy. With a focus on cancer immunology, we summarize the clinical trials of ICIs in ccRCC, the molecular and cellular correlates of these clinical trials, and the single-cell RNA sequencing studies to provide a comprehensive overview of the immune landscape within the ccRCC tumor microenvironment, in particular in the context of ICI therapy. We will discuss potential molecular and cellular biomarkers that can be used to predict therapeutic responses in ccRCC patients.Several clinicopathological features of clear cell renal cell carcinomas (ccRCC) contribute to make an “atypical” cancer, including resistance to chemotherapy, sensitivity to anti-angiogenesis therapy and ICIs despite a low mutational burden, and CD8+ T cell infiltration being the predictor for poor prognosis–normally CD8+ T cell infiltration is a good prognostic factor in cancer patients. These “atypical” features have brought researchers to investigate the molecular and immunological mechanisms that lead to the increased T cell infiltrates despite relatively low molecular burdens, as well as to decipher the immune landscape that leads to better response to ICIs. In the present study, we summarize the past and ongoing pivotal clinical trials of immunotherapies for ccRCC, emphasizing the potential molecular and cellular mechanisms that lead to the success or failure of ICI therapy. Single-cell analysis of ccRCC has provided a more thorough and detailed understanding of the tumor immune microenvironment and has facilitated the discovery of molecular biomarkers from the tumor-infiltrating immune cells. We herein will focus on the discussion of some major immune cells, including T cells and tumor-associated macrophages (TAM) in ccRCC. We will further provide some perspectives of using molecular and cellular biomarkers derived from these immune cell types to potentially improve the response rate to ICIs in ccRCC patients.

Immune Checkpoint Inhibitor Therapy in Colorectal Cancer-The Role of Cellular Pathology.

Colorectal cancer (CRC) is a common malignancy with a worldwide distribution. Despite bowel cancer screening programmes, the management of patients with metastatic disease is still an important and challenging problem. Immune checkpoint inhibitor (ICI) therapy is a well-established treatment in several cancers, eg, malignant melanoma and non-small cell lung carcinoma and is used in metastatic disease. The principle of this treatment is to use monoclonal antibodies to block the immune tolerance that commonly develops to tumor cells, therefore allowing host T-cell immunity to recognise and lyse cancer cells. The cellular receptors most commonly targeted by ICI therapy are cytotoxic T-lymphocyte-associated protein-4 and the programmed death 1/programmed death ligand 1 system. This review provides a scientific background to current ICI therapy and discusses the factors that predict response to this treatment. This is followed by a description of the emerging evidence for the use of ICI therapy in CRC and the utility of cellular pathology in stratifying patients for this treatment, especially when the systemic disease is present.

Non-invasive measurement of PD-L1 status and prediction of immunotherapy response using deep learning of PET/CT images

BackgroundCurrently, only a fraction of patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) experience a durable clinical benefit (DCB). According to NCCN guidelines, Programmed death-ligand...

Immune checkpoint inhibitor use in patients with end-stage kidney disease: an analysis of reported cases and literature review.

Immune checkpoint inhibitors (ICIs), immunomodulatory antibodies that are used to enhance the immune system, have substantially improved the prognosis of patients with advanced malignancy. As the use of ICI therapy becomes increasingly widespread across different types of cancer, their use in patients receiving dialysis is likely to increase. In this review we summarize the current literature on the use of ICIs in end-stage kidney disease (ESKD) patients and provide aggregate data from reported cases and series. Based on available pharmacological information, ICIs require no dosing adjustment in ESKD patients. Analysis of the reported cases in the literature demonstrates a similar incidence of immune-related adverse events in patients with ESKD receiving dialysis as compared with the general population (49%). Severe reactions graded as 3 and 4 have been seen in 15 patients (16%). As such, it is important that these patients are monitored very closely for immune-related adverse events; however, the risk of these adverse events should not preclude patients on dialysis from receiving these therapies. Cancer remission (complete and partial) was seen in close to 30% of patients, stable disease was seen in 28% and progression of disease in ∼36%. One-third of the patients died. Urothelial and renal cell cancer represented approximately half of all treated cancers and accounted for ∼50% of all deaths reported. Additional data in the dialysis population with the use of ICIs and involvement in prospective studies are needed to better assess outcomes, particularly within specific cancer types.

Neurologic Adverse Events of Immune Checkpoint Inhibitors: A Systematic Review.

To define the clinical characteristics, management, and outcome of neurologic immune-related adverse events (n-irAEs) of immune checkpoint inhibitors (ICIs). Systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 694 articles were identified. Two hundred fifty-six articles, with 428 individual patients, met the inclusion criteria. Reports regarding neuromuscular disorders (319/428, 75%) were more frequent than those on CNS disorders (109/428, 25%). The most common n-irAEs reports were myositis (136/428, 32%), Guillain-Barré syndrome and other peripheral neuropathies (94/428, 22%), myasthenic syndromes (58/428, 14%), encephalitis (56/428, 13%), cranial neuropathies (31/428, 7%), meningitis (13/428, 3%), CNS demyelinating diseases (8/428, 2%), and myelitis (7/428, 2%). Other CNS disorders were detected in 25/428 (6%) patients. Compared with the whole sample, myasthenic syndromes were significantly more Ab positive (33/56, 59%; p < 0.001). Anti-programmed cell death protein 1/programmed cell death ligand 1 was more frequent in myasthenic syndromes (50/58, 86%; p = 0.005) and less common in meningitis (2/13, 15%; p < 0.001) and cranial neuropathies (13/31, 42%; p = 0.005). Anti-cytotoxic T-lymphocyte antigen-4 ICIs were more frequent in meningitis (8/13, 62%; p < 0.001) and less common in encephalitis (2/56, 4%; p = 0.009) and myositis (12/136, 9%; p = 0.01). Combination of different ICIs was more frequent in cranial neuropathies (12/31, 39%; p = 0.005). Melanoma was more frequent in patients with peripheral neuropathies (64/94, 68%; p = 0.003) and less common in encephalitis (19/56, 34%; p = 0.001). The highest mortality rate was reached in myasthenic syndromes (28%). Considering the increasing use of ICI therapy in the forthcoming future, this information can be valuable in assisting neurologists and oncologists in early n-irAEs diagnosis and treatment.

New Insights into Mechanisms of Immune Checkpoint Inhibitor-Induced Cardiovascular Toxicity.

The review aims to summarize the present knowledge about cardiovascular toxicities associated with immune checkpoint inhibitors (ICI) and dissect underlying mechanism associated with individual cardiovascular toxicity. Widespread use of ICI therapy has allowed for increasing recognition of a wide spectrum of immune-related adverse events that leave all organ systems vulnerable. Immune-mediated cardiovascular toxicities, initially thought to be rare, are more often being reported and present considerable challenges due to their non-specific clinical presentation, potential to have a fulminant progression, and overlap with other cardiovascular and general medical illnesses. Myocarditis is the most common manifestation of ICI-associated cardiovascular toxicity. Pericardial diseases, vasculitis, Takotsubo syndrome, conduction abnormalities, and destabilization of atherosclerotic lesions constitute other significant adverse events. At this stage, mechanisms underlying fundamental biology of cardiac toxicity have not been studied comprehensively and there remain gaps of knowledge in the current literature concerning the underlying pathomechanisms. It is hypothesized that immune-mediated myocarditis is a result of an exaggerated adaptive immune response against shared epitopes in the myocardium and tumor cells. Further, underlying mechanism of other cardiovascular toxicities is still unclear, further compounded by sparsity of epidemiological data. It is paramount to understand the mechanisms behind ICI-induced cardiovascular toxicities to develop appropriate treatment and prevention strategies and minimize the morbidity and mortality of cancer patients undergoing ICI therapy.

SAT0536 IMMUNE CHECKPOINT INHIBITOR THERAPY IN PATIENTS WITH PREEXISTING SARCOIDOSIS

Background:Immune checkpoint inhibitors (ICI) have changed the treatment landscape of many cancer types, but are also associated with development of immune-related adverse events, includingde novosarcoid like reactions. However, little is known about the use of ICI therapy in patients with preexisting sarcoidosis as patients with preexisting autoimmune diseases have been systematically excluded from clinical trials of ICI therapy due to concerns of heightened toxicities. Emerging research suggests that ICI therapy can be considered in some patients with autoimmune diseases.1Objectives:To determine the risk of sarcoidosis exacerbation or flare in patients with preexisting sarcoidosis receiving ICI therapy.Methods:We conducted a retrospective cohort study of patients seen at The University of Texas MD Anderson Cancer Center between 2016-2019. Patients were included in the cohort if they received one of 7 ICI therapies (ipilimumab, nivolumab, pembrolizumab, durvalumab, avelumab, atezolizumab, or cemiplimab) and had an International Classification of Disease version 10 code of sarcoidosis (D86.*), prior to the ICI initiation, with diagnosis confirmed in medical record by treating physicians. A sarcoidosis diagnosis was considered “possible” if the medical record documented a history of sarcoidosis, “probable” if a history of biopsy proven sarcoidosis was mentioned, and “definitive” if histological evidence was available. Frequency of flares and outcomes of patients after receiving ICI were collected.Results:During the study timeframe a total of 32 patients with preexisting sarcoidosis received ICI therapy. Nine patients (28%) had a definitive diagnosis of sarcoidosis, 12 (37%) had a probable diagnosis and 11 (35%) had a possible diagnosis of sarcoidosis. The mean time between diagnosis of sarcoidosis and initiation of ICI therapy was 13 years (range: &lt;1 to 51 years). Twenty-seven patients (84%) received monotherapy and five patients (16%) received combination or sequential ICI therapy. Of the 32 patients, one patient with a 20-year remote history of sarcoidosis, never treated, developed a clinically symptomatic exacerbation of sarcoidosis one month after the initial dose of atezolizumab, with increased hilar nodules on imaging, skin nodules, arthritis and uveitis. Biopsy of a lymph node showed non-necrotizing granulomas, and biopsy of the skin panniculitis. The patient also developed colitis thought to be an immune-related adverse event. Atezolizumab was discontinued after 3 doses. Patient was treated with prednisone and azathioprine.Conclusion:Patients with a remote history of stable sarcoidosis at the time of ICI therapy infrequently develop a flare of their sarcoidosis. The risk of flares in patients with active sarcoidosis requiring immunosuppression at the time of ICI initiation is unknown.

Treatment of immune checkpoint inhibitor-induced inflammatory arthritis.

This review summarizes the current evidence on treatment strategies for inflammatory arthritis because of cancer treatment with immune checkpoint inhibitors (ICI), prognosis of ICI-induced arthritis, and management of patients with preexisting inflammatory arthritis receiving ICI therapy. Inflammatory arthritis is the most common rheumatic immune-related adverse event observed in patients receiving ICI therapy. Most patients can successfully be treated with low doses of corticosteroids or conventional synthetic disease modifying anti-rheumatic drugs (DMARDs). A small minority will develop severe symptoms requiring biologic therapy including TNF inhibitors and IL-6 receptor inhibitors. Many cases of inflammatory arthritis will resolve with cessation of ICI therapy. Some patients will develop persistent arthritis despite discontinuation. Patients with preexisting inflammatory arthritis (e.g. rheumatoid arthritis) commonly flare on ICI therapy, but can usually be managed with corticosteroids. Inflammatory arthritis following ICI therapy for cancer is relatively common and the practicing rheumatologist should be able to recognize and manage it in conjunction with Oncology. The majority of patients respond to corticosteroids, but some will need treatment with conventional synthetic or biologic DMARDs. Additional studies should investigate the effects of immunosuppression on tumor response and the use of ICI therapy in patients with preexisting autoimmune disease.

Cardiac Complications in Immune Checkpoint Inhibition Therapy.

Immune checkpoint inhibitors (ICIs) have changed the treatment landscape of advanced cancers. Unfortunately, these agents can induce a wide spectrum of immune-related adverse events (irAEs) through activation of immune responses in non-target organs, including the heart. As the clinical use of ICI therapy increases rapidly, management of irAEs is becoming extremely important. The most commonly presented cardiac irAE is myocarditis. Histopathologically, T-cell (with a predominance of CD8+ cells) and macrophage infiltration in the myocardium is typically observed in ICI-associated myocarditis. Other presentations of cardiac irAEs include congestive heart failure, Takotsubo cardiomyopathy, pericardial disease, arrhythmias, and conduction disease. Although cardiac irAEs are relatively rare, they can be life-threatening. Hence, cardiologists and oncologists should be vigilant for these presentations.

Association of the adoption of immune checkpoint inhibitor therapy (ICT) with prevalence of tumor mutation burden (TMB) in sixteen cancer types.

e18557 Background: Tumor Mutation Burden (TMB) is an emerging biomarker for response to immune checkpoint inhibitor therapy (ICT). PDL1 is still the only companion diagnostic test for ICT. We sought to examine the relationship between the use of ICT based on real world prescription data relative to key FDA approval dates to TMB prevalence data based on whole exome sequencing (WES). Methods: Treatment plans submitted through a proprietary web-based application to obtain automated precertification for first, second, and third line therapies for 16 tumor types were retrospectively reviewed for ICT use before and after key ICT approval dates. These usage rates were then compared to the frequency of high TMB in respective tumor types as determined by a retrospective analysis of data from a commercial DNA tumor:normal and RNAseq platform where 992 samples were identified with paired DNA(WGS or WES)/RNAseq NGS. “High” vs “low” mutation burden was assigned with a threshold of 200 non-synonymous mutations. Results: High TMB frequency ranged between 5%(ovary)-52%(melanoma). ICT usage ranged between 0%-2%(melanoma) from 2011 through 2014, 0%-56%(melanoma) between 2015 and May 2017, and 0%-66%(melanoma) from May 2017 to February 2018. The rate of ICT usage increased by more than 15% since 2015 in head and neck, kidney, liver, lung, and melanoma. However, in kidney, liver, and melanoma, the usage rates since May 2017 are 18%, 10%, and 13% greater than the frequency of high TMB in those tissue types. Conversely, usage rates are 11-23% lower than high TMB frequency in bladder, breast, colon, lung, rectal, and uterine cancer. Conclusions: In this retrospective analysis using WES data to evaluate the correlation of high TMB frequency tumor types and ICT use, we found ICT use increased across most tumor types after 2014. However, the rate of use is lower than the prevalence of high TMB in many cancers (including lung). As ICT therapy is associated with better quality of life and equal to better overall survival than chemotherapy, more aggressive identification of prospective ICT patients through NGS exome assessment of TMB could be warranted.

Abstract PD6-09: The immune microenvironment in hormone receptor-positive breast cancer patients and relationship to treatment outcome following preoperative chemotherapy plus bevacizumab

Abstract Background: Hormone receptor-positive (HR+) tumors have fewer tumor-infiltrating lymphocytes (TILs) and lower response rates to immune checkpoint inhibitors (ICI), either as single agents or in combination with chemotherapy, than triple negative cancers. However, some HR+ cancers do respond to ICI and biomarkers that accurately reflect the immune microenvironment may help guide the use of ICI therapy. Prior evidence suggests that macrophage-related immune pathways may be relevant to the pathophysiology of HR+ BC. Methods: HR+/HER2- patients were identified from a prospective trial of preoperative bevacizumab (preop bev) followed by bev with adriamycin/cyclophosphamide/paclitaxel dose-dense chemotherapy (chemo). Tumor samples were collected at diagnosis and surgery (pre-tx and post-tx), and PD-L1 expression (by immunohistochemistry), TILs, and Nanostring PanCancer Immune Profiling Panel were evaluated on both pre-tx and post-tx specimens. Pre-tx whole transcriptome sequencing was performed. Pathologic response at surgery was centrally assessed by Miller-Payne (MP) and residual cancer burden (RCB) scores. An immune score was calculated for each pre-tx specimen by integrating 10 published immune signatures. Immune cell subsets were inferred from bulk transcriptional data using CIBERSORT and immune cell-specific signatures from MSigDB. Results: 55 patients who received trial therapy and had at least 1 evaluable specimen were included for analysis. Pre-tx TILs and tumor PD-L1 (tPD-L1) scores are shown in the table. 18% of pre-tx tumors had “high” (≥10%) TILs and “high” TILs were associated with significantly higher immune signature score (p=0.004). Immune score correlated highly with proportion of CIBERSORT anti-tumor M1 macrophages as well as CD8 T-cell signatures (r&amp;gt;0.65 and p&amp;lt;0.001). Higher pre-tx TILs, tPD-L1, or immune score were each significantly associated with more favorable RCB and MP in unadjusted analyses (all Spearman p&amp;lt;0.01 for pathologic markers; ANOVA p&amp;lt;0.04 for immune score). After adjustment for age and tumor grade, higher pre-tx TILs and tPD-L1 were associated with favorable RCB (p&amp;lt;0.01 for both), and higher pre-tx tPD-L1 correlated with favorable MP (p=0.03). Pathologic complete response occurred in 4 pts; all 4 had high pre-tx TILs, pre-tx tPD-L1, or both. Among patients with residual disease, large changes (&amp;gt;5%) in TILs or tPD-L1 from pre-tx to post-tx were rare: 2 pts each had large changes in TIL or tPD-L1 score (N=38/N=31 pairs, respectively). Conclusions: High levels of tumor-lymphocyte interaction were seen in only a minority of untreated HR+ breast tumors, and did not typically change with chemo plus bev. An immune score derived from bulk RNAseq correlated with histological observations in these specimens. Nonetheless, TILs, tPD-L1, and signature-derived immune score were significantly associated with pathologic response to preop treatment in HR+ disease. Early data suggest that the role of M1 macrophages in HR+ tumors warrants further investigation. ScoreTILs (N=50 evaluable)Tumor PD-L1 (N=51)0%0 pts (0%)28 pts (55%)&amp;gt;0-5% (low)19 (38%)18 (35%)&amp;gt;5-10% (intermediate)22 (44%)3 (6%)&amp;gt;10% (high)9 (18%)2 (4%) Citation Format: Waks AG, Stover DG, Barry W, Dillon D, Gjini E, Rodig SJ, Brock J, Baltay M, Savoie J, Winer EP, Krop I, Tolaney SM. The immune microenvironment in hormone receptor-positive breast cancer patients and relationship to treatment outcome following preoperative chemotherapy plus bevacizumab [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD6-09.