Virtual Library
Start Your Search
R. Perez-Soler
Author of
-
+
OA 13 - Immuno-Biology (ID 677)
- Event: WCLC 2017
- Type: Oral
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:Hiroyuki Suzuki, Scott N. Gettinger
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 301 + 302
-
+
OA 13.03 - Wide Expression of Alternative Immune Checkpoint Molecules, B7x and HHLA2, in PD-L1 Negative Human Lung Cancers (ID 10020)
11:20 - 11:30 | Author(s): R. Perez-Soler
- Abstract
Background:
Immunotherapy targeting the PD-1/PD-L1 pathway has dramatically changed the treatment landscape of non-small-cell lung carcinoma (NSCLC). We previously demonstrated that HHLA2, a recently identified B7 family immune inhibitory molecule, was widely expressed in NSCLC. To better understand the immune evasion mechanisms within the tumor microenvironment, we compared the expression profiles and functional roles of PD-L1 with potential alternative immune checkpoints, B7x and HHLA2.
Method:
Expression was assessed by immunohistochemistry using tissue microarrays consisting of 392 NSCLC tumor tissues (mostly resected stage I to III), including 195 tumors in the discovery (D) set and 197 cases in the validation (V) set. Positive PD-L1 cases were defined as samples with percentage of tumor cells revealing membranous staining of PD-L1 ≥ 1% with SP142 antibody. Human T cells were purified from eleven donors. Control human IgG, human PD-L1-Ig, human B7x-Ig and human HHLA2-Ig were used to determine the effects of PD-L1, B7x and HHLA2 on T cell proliferation and cytokine production [Human Th Cytokine Panel: IL-5, IL-13, IL-2, IL-6, IL-9, IL-10, IFN-γ, TNF-α, IL-17F, IL-17A, IL-4, IL-21 and IL-22].
Result:
PD-L1 expression was detected in 25% and 31% of tumors in the D and V sets respectively, and was associated with higher stage and lymph node involvement in both cohorts. Multivariate analysis further showed that stage, TIL status and lymph node involvement were independently associated with PD-L1 expression. B7x was expressed in 69% and 68% of cases, while HHLA2 was positive in 61% and 64% of tumors in the two sets. Triple positive expression was detected in 13% whereas triple negative in 15% of cases. The double-expression of PD-L1 with B7x or HHLA2 was rare, 6% and 3% respectively. Interestingly, the majority (78%) of PD-L1 negative cases expressed B7x, HHLA2 or both. Moreover, the triple positive group correlated with more TIL infiltration as compared to the triple negative group (P = 0.0175). At the same concentration, B7x-Ig and HHLA2-Ig inhibited TCR-mediated proliferation of both CD4 and CD8 T cells significantly more robustly than PD-L1-Ig. All three significantly suppressed a variety of cytokine production by T cells.
Conclusion:
The majority of PD-L1 negative lung cancer cases express alternative immune checkpoint molecules (B7x, HHLA2 or both). The potential role of the B7x/HHLA2 pathway in mediating immune evasion in PDL1 negative tumors deserves to be explored to provide the rationale for an effective immunotherapy strategy in these tumors.
Information from this presentation has been removed upon request of the author.
-
+
P1.07 - Immunology and Immunotherapy (ID 693)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P1.07-027 - PD-L1 Expression Analysis in African American (AA) and Hispanic Lung Cancer Patients at a Minority-Based Academic Cancer Center (ID 9734)
09:30 - 09:30 | Author(s): R. Perez-Soler
- Abstract
Background:
PD-L1 testing has been incorporated into the standard treatment paradigm given recent immunotherapy approvals for metastatic lung cancer (LC). Minority populations are notoriously under-represented in large immunotherapy clinical trials. Thus, we examined PD-L1 expression profiles in a minority-based academic cancer center. Among 989 patients with newly diagnosed LC at Montefiore Medical Center (MMC) from 2014-2015, 330 (33%) were AA and 195 (20%) were Hispanic.
Method:
Retrospective chart review was conducted to determine PD-L1 expression patterns between 1/1/14-6/19/17 at MMC. PD-L1 testing was performed using 22C3pharmDx IHC and positivity was defined as >/=1%. Chi-squared statistical analysis was performed with SPSS. All statistical tests were two-sided.
Result:
We identified 92 patients who had PD-L1 testing, with a median age of 66. Based on race, 43 (46.7%) were AA, 20 (21.7%) were White, 20 (21.8%) were Other and 9 (9.8%) were race unknown. Based on ethnicity, 27 (29.3%) were Hispanic, 54 (58.7%) were non-Hispanic and 11 (12%) were ethnicity unknown. Adenocarcinoma was the dominant histology (61%). Nine (9.8%) were EGFR mutant and 1 (1.1%) had an ALK rearrangement. Fresh tissue was used in 50% of cases. PD-L1 TPS >50% was found in 30 (33%), 1-49% in 22 (24%) and <1% in 39 (42%). At time of this analysis, 29 (32%) had received immunotherapy. In the racial analysis, 9 were excluded due to unknown race. Amongst the 43 AA patients, 28 (65%) were PD-L1 positive, and 15 (35%) were negative compared to the 40 non-AA patients which were PD-L1 positive in 20 (50%) and negative in 20 (50%). AAs trended toward increased PD-L1 positivity compared to non-AAs although it was not significant (p=0.163). In the ethnicity analysis, 11 were excluded due to unknown ethnicity. Amongst the 27 Hispanic patients, 11 (40.7%) were PD-L1 positive and 16 (59.3%) were negative compared to the 54 non-Hispanic patients who were PD-L1 positive in 37 (68.5%) and 17 (31.5%) were negative. Analysis suggests there is a negative association between Hispanic ethnicity and positive PD-L1 testing (p=0.016).
Conclusion:
This is the first known report on PD-L1 expression in AA and Hispanic patient populations. We found that Hispanics had significantly more PD-L1 negative cases compared to non-Hispanics. Correlation with response to immunotherapy is ongoing. Continued research and focus on minority populations will further help to narrow known health disparities based on race and ethnicity.
-
+
P2.13 - Radiology/Staging/Screening (ID 714)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P2.13-008 - Lung Cancer Screening Improves Mortality: Examining Screening Patterns in an Urban Underserved Community (ID 9134)
09:30 - 09:30 | Author(s): R. Perez-Soler
- Abstract
Background:
The landmark Lung Cancer Screening (LCS) Trial demonstrated a significant reduction in mortality. However, European LCS trials have not confirmed such benefit. We examined the impact of LCS-led diagnosis on the mortality of newly diagnosed lung cancer patients at an urban medical center.
Method:
Medical records of patients diagnosed with primary lung cancer for the period 2013-2015 (n=638) were reviewed to identify those who had an established primary care provider (PCP), were LCS-eligible/ non LCS-diagnosed, and LCS-eligible/LCS-diagnosed as per the United States Preventative Services Task Force (USPSTF) guidelines. Baseline characteristics between LCS-eligible/non-diagnosed patients and LCS-eligible/diagnosed patients were analyzed using chi-squared and Wilcoxon-Mann-Whitney tests. Kaplan-Meier curves were generated, and predictors of overall survival were evaluated using Cox proportional hazards modeling.
Result:
134 primary lung cancer patients had an established PCP and were LCS-eligible; 19/134 (14%) were LCS-diagnosed. LCS-eligible/LCS-diagnosed patients were of younger age (p=0.03), English-speaking (p=0.03), of higher socioeconomic status (p=0.02), active smokers (p<0.01), and had earlier disease stages (p=0.02) than LCS-eligible/non-diagnosed patients. All-cause mortality was significantly lower in LCS-eligible/diagnosed patients compared to LCS-eligible/non-diagnosed patients (p=0.03). Disease stage was found to be the main factor associated with higher mortality by multivariate regression analysis (HR: 6.13, stage 4 vs. stage 1-2, p<0.01).
Conclusion:
To our knowledge, this is the first report of lung cancer mortality differences in LCS eligible patients as a function of them undergoing or not LCS in a single-center setting since the inception of the USPSTF guidelines. Patients with an LCS-led diagnosis had a reduced mortality, probably as a result of having an earlier disease stage, which echoes the findings of large prospective LCS trials. LCS-led diagnosis rates remain low among lung cancer patients. Fully implementing the USPSTF guidelines constitutes a great unrealized opportunity to decrease lung cancer mortality.
